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Purpose: Research has shown that exposure to anesthesia might increase the risks of cognitive impairments and learning difficulties. MiR-125b-5p contributed to anesthesia-induced hippocampal apoptosis. However, the role of miR-125b-5p in sevoflurane-induced cognitive impairments remains unclear., Methods: Firstly, sevoflurane was used to establish a rat model and cognitive impairment was detected by the Morris water maze (MWM) test. The hippocampus was observed by HE staining. The lentivirus-miR-125b-5p antagomiR was transfected into rats to decrease miR-125b-5p. The interaction between miR-125b-5p and LIM domain kinase 1 (LIMK1) was confirmed by the luciferase reporter assay. The mRNA and expression levels of related genes and mRNA were examined by the Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and western blot., Results: Sevoflurane induced the cognitive dysfunction presenting with longer latency time and few platform crossings in rats. Moreover, miR-125b-5p was observed to be up-regulated in both sevoflurane-anesthesia rats and sevoflurane-treated SH-SY5Y cells. More importantly, a decrease in miR-125b-5p could prevent sevoflurane-induced hippocampal apoptosis and inflammation in rats. Moreover, LIMK1 was the target gene of miR-125b-5p. Interestingly, si-LIMK1 could restore the sevoflurane-induced cell apoptosis in SH-SY5Y cells, which was alleviated by miR-125b-5p inhibitor. Finally, the miR-125b-5p inhibitor shortened the time to find the platform and increased the number of platform crossings compared to sevoflurane-anesthesia rats in the Morris water maze test. At the same time, the expression of LIMK1 was dramatically increased., Conclusion: Altogether, these findings suggested that miR-125b-5p inhibitor could protect against the sevoflurane-induced cognitive impairments by targeting LIMK1., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The aim of this review is to discuss the research presented in a symposium entitled "Current progress in characterizing therapeutic strategies and challenges in experimental CNS injury" which was presented at the 2016 International Behavioral Neuroscience Society annual meeting. Herein we discuss diffuse and focal traumatic brain injury (TBI) and ensuing chronic behavioral deficits as well as potential rehabilitative approaches. We also discuss the effects of stress on executive function after TBI as well as the response of the endocrine system and regulatory feedback mechanisms. The role of the endocannabinoids after CNS injury is also discussed. Finally, we conclude with a discussion of antipsychotic and antiepileptic drugs, which are provided to control TBI-induced agitation and seizures, respectively. The review consists predominantly of published data., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Previous study has demonstrated lancao decoction (LC), a traditional Chinese medicine (TCM) fomula and recorded in "Huangdineijing", has a therapeutic effect on cognitive impairment (early clinical manifestations of alzheimer's disease (AD), which suggests that LC may have potential therapeutic advantages for AD. Whether LC has the therapeutic effect on AD and its potential mechanisms were still further indicated., Aim of the Study: In this study, we aimed to uncover the potential advantage and neuronal mechanisms of LC in the treatment of AD in APP/PS1 mice in the hippocampus., Methods and Materials: We chose APP/PS1 mice to combing with behavioral tests including morris water maze (MWM) or y-maze to determine the role of LC in the therapeutic actions of AD. Network pharmacology was used to screen potential targets and pathways involving in LC's treatments of AD. Western blot was used to detect the phosphorylated expressions of proteins in hippocampus in APP/PS1 mice in the hippocampus. Pharmacological interventions were used to elucidate the relationship between the role of LC in the treatment of AD and the pathway, as well as the upstream and downstream interactions with neuronal activities., Results: According to our previous LC effective dose (2.5 g/kg), the dose was also able to significantly reduce the latency to the platform, and significantly increase the number of crossing times and time spend in the target quadrant in APP/PS1 mice in MWM, which was consistent with donepezil (DON) after 14 days chronic treatments. Network pharmacology showed that PI3K/AKT and MAPK pathways were closely associated with LC's treatments of AD, and protein autophosphorylation played a role in this process. The phosphorylated expressions of PI3K and AKT were obviously reduced in APP/PS1 mice in the hippocampus, which were both reversed by LC or DON. The phosphorylated expressions of MAPK including P38, JNK and ERK were also significantly reduced in APP/PS1 mice hippocampus, but only the phosphorylated expression of ERK was reversed by LC or DON. Inhibiting the activities of PI3K/AKT pathway by LY294002 blocked LC's improvement of behavioral deficits in APP/PS1 mice, including reducing latency to platform and increasing the number of crossings time in MWM in APP/PS1 mice, which also blunted LC's up-regulated phosphorylated expressions of PI3K, AKT and ERK in the hippocampus. Moreover, suppressing the activities of ERK by PD98059 also blocked LC's improvement of AD-related behavioral deficits including decreasing latency to new arm and increasing time in new arm in y-maze test, which also inhibited LC's enhancement of synaptic proteins (PSD95 and synapsin1) in the hippocampus and the number of EGR1-positive cells in the hippocampal dentate gyrus (DG)., Conclusions: Take together, our study revealed that LC had the therapeutic effects on AD by activating the PI3K/AKT pathway to enhance ERK activity and further strengthened neuronal activities in the hippocampus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Neonatal hypoxic-ischemic encephalopathy (HIE) is a severe neurological injury during infancy, often resulting in long-term cognitive deficits. This study aimed to investigate the neuroprotective effects of Edaravone (EDA), a free radical scavenger, and elucidate the potential role of brain-derived neurotrophic factor (BDNF) in mediating these effects in neonatal HIE rats. Using the Rice-Vannucci model, HIE was induced in neonatal rats, followed by immediate administration of EDA after the hypoxic-ischemic insult. To examine the role of BDNF, a separate group of rats received intrahippocampal injections of a lentiviral vector for BDNF knockdown prior to the induction of HIE and subsequent EDA treatment. Neuronal survival and apoptosis in the hippocampal region were assessed by immunofluorescence and TUNEL staining, respectively. BDNF expression levels in the hippocampus were analysed using enzyme-linked immunosorbent assay (ELISA). Cognitive function was evaluated using the Morris water maze (MWM) and Y maze tests. Results demonstrated that EDA significantly reduced hippocampal neuronal apoptosis and death, increased neuronal survival, and enhanced BDNF expression compared to the control group. However, the therapeutic effects of EDA were mitigated in the BDNF knockdown group, indicating a crucial role of BDNF in mediating the neuroprotective effects of EDA. Behavioural testing confirmed that EDA treatment significantly improved spatial learning and memory abilities in HIE rats, but these improvements were not observed in rats with BDNF knockdown. In conclusion, our study suggests that EDA treatment mitigates hippocampal neuronal death and improves cognitive dysfunction in HIE rats primarily by upregulating BDNF expression. These findings provide experimental support for the potential application of EDA in the treatment of HIE and highlight the essential role of BDNF in neuroprotection and cognitive recovery post-HIE., (© 2025 International Society for Developmental Neuroscience.)

Background: The aim of this study was to establish an iron overload rat model to simulate the elevated iron levels in patients with thalassemia and to investigate the potential association between hippocampal iron deposition and cognition., Methods: Two groups of iron overloaded rats and one group of control rats were used for this study. The Morris water maze (MWM) was used to test spatial reference memory indicated by escape latency time and number of MWM platform crossings. The magnetic susceptibility value of the hippocampal tissue, a measure of iron deposition, was assessed by quantitative susceptibility mapping (QSM) and was correlated with spatial reference memory performance. The iron content in hippocampal tissue sections of the rats were assessed using diaminobenzidine (DAB)-enhanced Perl's Prussian blue (PPB) staining., Results: The rat groups with iron overload including the Group H and Group L had higher hippocampal magnetic susceptibility values than the control rat group, i.e., Group D. In addition, the iron overloaded groups had longer MWM escape latency than the control group, and reduced number of MWM platform crossings. There was a positive correlation between the mean escape latency and the mean hippocampal magnetic susceptibility value, a negative correlation between the number of platform crossings and the mean hippocampal magnetic susceptibility value, and a negative correlation between the number of platform crossings and the latent escape time in Group H and Group L., Conclusion: This rat model simulating iron overload in thalassemia showed hippocampal iron overload being associated with impairment of spatial reference memory. QSM could be used to quantify brain iron overload in vivo, highlighting its potential clinical application for assessing cognitive impairment in patients with thalassemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Fetal alcohol syndrome (FAS) can occur because of high amount of alcohol intake during pregnancy and is characterized by both physical and neurological problems. Children diagnosed with FAS have difficulties in learning, memory, and coordination. Hippocampus has a major role in memory and learning. We aimed to determine whether alcohol exposure during pregnancy had any effect on offspring by evaluating learning ability as well as oxidative stress and autophagy in the hippocampus and cortex tissues of litters. Attention was also paid to sex differences. To do so, TRPM2, Beclin1, p62, LC3B, IBA1, parvalbumin, GAD65, and mGluR5 expression levels were evaluated by immunohistochemistry. Lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels, as well as total oxidant (TOS) and total antioxidant (TAS) status were determined by ELISA. Learning experiments were evaluated by the Morris water maze (MWM) test. Our findings demonstrated that IBA1, LC3B, GAD65, and mGluR5 expression levels were higher in female rats of the chronic alcohol exposure (CAE) model. Our IHC results revealed that TRPM2 expression levels were significantly increased in both males and females in the CAE group. Likewise, TAS was lower, and TOS was higher in CAE animals. Moreover, MWM outcomes supported a learning deficiency in CAE litters compared to controls and indicated that female offspring outperformed males in learning experiments. Therefore, our results revealed the detrimental effects of alcohol exposure during pregnancy on autophagy signaling in the hippocampus and cortex tissue of litters, which could affect the learning ability of animals., (© 2024 The Author(s). Environmental Toxicology published by Wiley Periodicals LLC.)

Luffa cylindrica (L.), is a medicinal plant aimed to investigate the efficacy of the alkaloid-rich fraction (ARF) extracted from L. cylindrica. The study employed behavioural analysis of rat using Morris water maze (MWM), biochemical analysis of apoptotic proteins, Immunohistochemistry of caspase 3 protein and network pharmacology approach. The ozone-induced group exhibited complex behavioral changes. Western blot analysis revealed altered expression of SOD2, Caspase 3, and Cytochrome C which play integral roles in oxidative stress, apoptosis, and mitochondrial function. Histopathological analysis of the hippocampus further supported the neuroprotective potential of L. cylindrica, demonstrating a reduction in neuropathological lesions and improved memory processes. Network Pharmacology showed the implication of GSK3β in neuronal damage. ARF showed promise in preventing further neuronal damage. In summary, this comprehensive study sheds light on its potential in neuroprotective applications by in vivo behavioral and molecular analyses. It provides a holistic understanding of the medicinal properties of ARF, encouraging further exploration for potential therapeutic interventions in neurological diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Diabetes-induced cognitive dysfunction (DCD) is a neurological disorder associated with diabetes, characterized by cognitive impairment driven by neuronal injury from chronic high glucose (HG) exposure. This study aims to elucidate the role and mechanisms of the X-linked inhibitor of apoptosis protein (XIAP)/thioredoxin-interacting protein (TXNIP) in hippocampal neuron cell death and cognitive function within DCD models. A diabetic rat model was established using a high-fat/sucrose diet and streptozotocin injection. Primary hippocampal neurons were stimulated with HG to mimic diabetic conditions. Cognitive and memory functions were assessed using the Morris water maze (MWM) and novel object recognition test (ORT)., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Objectives: Endoplasmic reticulum (ER) stress-induced protein homeostasis perturbation is a core pathological element in the pathogenesis of neurodegenerative diseases. This study aims to clarify the unique role played by C/EBP homologous protein (CHOP) as a biomarker of the unfolded protein response (UPR) in the etiology of chronic pain and related cognitive impairments following chronic constrictive nerve injury (CCI)., Methods: The memory capability following CCI was assessed utilizing the Morris water maze (MWM) and fear conditioning test (FCT). Activation of the UPR was quantified by assessing levels of CHOP and key ER stress sensors. The terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay and the levels of cleaved caspase-3 were utilized to assess apoptosis level. Synaptic plasticity was assessed via a modified Golgi-Cox staining method, and long-term potentiation (LTP) measurements were taken. Neuronal activity was determined by immunofluorescence and fiber photometry. Knockdown of CHOP and alleviation of ER stress were selectively induced by LV-Ddit3-shRNAs and the chemical chaperone 4-phenylbutyric acid (4-PBA), respectively., Results: Mice subjected to CCI displayed enduring pain and cognitive impairments evident on Days 21-28 post-surgery. Following CCI, changes in the dorsal CA1 (dCA1) manifested as ER dilation, upregulation of CHOP and upstream signaling molecules, reduced dendritic spine density, and PSD95 levels, and impaired LTP. Additionally, the co-localization of CaMKIIα/c-Fos and CaMKIIα dCA1 -mediated calcium signaling was significantly reduced, while the activation of CaMKIIα was found to mitigate cognitive impairments in CCI mice. Selective knockdown of CHOP enhanced synaptic plasticity and CaMKIIα neuron activity, while 4-PBA treatment alleviated ER stress, synergistically improving cognitive deficits associated with chronic pain., Conclusion: CCI-induced CHOP upregulation impairs dCA1 synaptic plasticity and neuronal activity, leading to chronic pain-related cognitive deficits., (© 2025 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Rationale: The accumulation of beta-amyloid peptide (Aβ) in the forebrain leads to cognitive dysfunction and neurodegeneration in Alzheimer's disease. Studies have shown that individuals with a consistently cognitively active lifestyle are less vulnerable to Aβ toxicity. Recent research has demonstrated that intrahippocampal Aβ can impact catecholaminergic release and spatial memory. Interestingly, exposure to novelty stimuli has been found to stimulate the release of catecholamines in the hippocampus. However, it remains uncertain whether repeated enhancing catecholamine activity can effectively alleviate cognitive impairment in individuals with Alzheimer's disease., Objectives: Our primary aim was to investigate whether repeated exposure to novelty could enable cognitive resilience against Aβ. This protection could be achieved by modulating catecholaminergic activity within the hippocampus., Methods: To investigate this hypothesis, we subjected mice to three different conditions-standard housing (SH), repeated novelty (Nov), or daily social interaction (Soc) for one month. We then infused saline solution (SS) or Aβ (Aβ 1-42 ) oligomers intrahippocampally and measured spatial memory retrieval in a Morris Water Maze (MWM). Stereological analysis and extracellular baseline dopamine levels using in vivo microdialysis were assessed in independent groups of mice., Results: The mice that received Aβ 1-42 intrahippocampal infusions and remained in SH or Soc conditions showed impaired spatial memory retrieval. In contrast, animals subjected to the Nov protocol demonstrated remarkable resilience, showing strong spatial memory expression even after Aβ 1-42 intrahippocampal infusion. The stereological analysis indicated that the Aβ 1-42 infusion reduced the tyrosine hydroxylase axonal length in SH or Soc mice compared to the Nov group. Accordingly, the hippocampal extracellular dopamine levels increased significantly in the Nov groups., Conclusions: These compelling results demonstrate the potential for repeated novelty exposure to strengthen the dopaminergic system and mitigate the toxic effects of Aβ 1-42 . They also highlight new and promising therapeutic avenues for treating and preventing AD, especially in its early stages., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest., (© 2024. The Author(s).)

To optimize the clinical approach to non-convulsive status epilepticus (NCSE), it is essential to gain insight into its long-term effects on cognition and behaviors. Here, we investigated limbic NCSE-induced hippocampal injury and behavioral deficits in peri-adolescent rats. NCSE was induced in P43 Sprague Dawleyrats with intrahippocampal subconvulsive doses of kainic acid (NCSE group, n = 14) under continuous epidural cortical electroencephalography (EEG). Controls received volume-matched saline (n = 18). Following one month of continuous EEG monitoring, rats were sequentially subjected (P73-91) to the open field, the Morris water maze (MWM), and the modified two-way active avoidance (MAAV). Rats were sacrificed at P91 to histologically assess hippocampal injury with NeuN (neuronal nuclei) staining, levels of GFAP (glial fibrillary acidic protein), and synaptophysin (Syp). Following kainic acid administration, the NCSE group experienced electroclinical seizures characterized by behavioral arrest and oromotor automatisms without tonic-clonic activity (latency: 15.93 ± 4.70 min, duration: 68.35 ± 17.97 min). There were no seizure recurrences in the rest of the long-term recordings. Compared to controls, NCSE rats had impaired place learning in the MWM, and lower rates of context-cued shock avoidance in the MAAV (p < 0.05). The NCSE and control groups had comparable hippocampal neuronal densities and GFAP levels, but NCSE rats had significantly lower hilar Syp levels. One episode of limbic NCSE during peri-adolescence results in later life hippocampal synaptic dysfunction and contextual learning deficits. These data suggest that the diagnosis and treatment of NCSE should be prompt., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Diabetes-associated cognitive dysfunction (DACD) is a chronic ailment that exerts a substantial influence on the overall well-being of individuals. The hippocampus assumes a pivotal role in the progression and sustenance of cognitive impairment. The identification of differentially expressed proteins (DEPs) in the hippocampus is crucial for understanding the mechanisms of DACD., Methods: A rat model of DACD was established by a high-fat diet combined with streptozotocin intraperitoneal injection. The Morris water maze (MWM), hematoxylin and eosin (H&E) staining, Nissl staining, and transmission electron microscope (TEM) were performed on the rats. The proteins expressed in the hippocampus were detected using 4D label-free quantitative proteomics. Four DEPs, namely Nptx1, Ptpmt1, Slc25a11, and Cpt1c, were validated using parallel reaction monitoring (PRM)., Result: Our study found that hippocampal lesions were present in the DACD rat models. There were 59 up-regulated and 98 down-regulated DEPs in the Model group compared to the Control group. We found that the levels of Nptx1, Ptpmt1, Slc25a11, and Cpt1c were elevated in the Model group, which are important for cell mitochondrial function. It should be noted that in our study, we only used PRM to validate the expression of these proteins. However, more evidence is needed to establish the relationship between these protein changes and DACD., Conclusion: Our research results may provide further insight into the molecular pathology of hippocampal injury in DACD. In addition, further studies and clinical trials are required to confirm our findings and establish a more conclusive molecular mechanism for DACD.

Vigorous research confirmed the anti-inflammatory, antioxidant, and antidementia effects of apigenin (Api). The present study evaluated the beneficial impacts of Api administration on behaviour, brain-derived neurotrophic factor (BDNF), Interleukin 6 (IL-6), oxidative stress, and inflammation induced by social isolation (SI) stress in rats. For this purpose, rats underwent a 28-day SI period followed by a 4-week oral Api treatment (50 mg/kg/day, PO). On Day 56, behaviour tests were performed, including an elevated plus maze (EPM), Morris water maze (MWM), and three-chamber social tests. The oxidative stress markers, IL-6, and BDNF levels were measured in the hippocampus. Our results showed that SI stress caused an increase in anxiety and a decrease in spatial memory, sociability, and social preference index. In addition, SI stress increased hippocampal levels of IL-6 and malondialdehyde (MDA) content, whereas it reduced the hippocampal BDNF level and superoxide dismutase (SOD) activities. Our study indicated that Api attenuates anxiety and causes improvements in spatial memory and social interaction. These desirable effects of Api might be related to amelioration in the BDNF level, IL-6, and oxidative stress biomarkers in the hippocampus., (© 2024 International Society for Developmental Neuroscience.)

Sleep fragmentation (SF) is increasingly recognized as a contributing factor to postoperative cognitive dysfunction (POCD). Given the critical roles of somatostatin (SST) interneurons, associated gamma-aminobutyric acid (GABA)ergic neurotransmitters, and hippocampal perfusion in sleep-related cognition, this study examined changes in these mechanisms in preoperative SF affecting POCD induced by anesthesia/surgery in aged male mice. The Morris water maze (MWM), novel object recognition (NOR), and Y maze tests were utilized to evaluate POCD. Arterial spin labeling (ASL) was employed to measure hippocampal regional cerebral blood flow (rCBF). In vitro assays quantified the levels of GABAergic metabolites-such as SST, neuropeptide Y (NPY), glutamic acid decarboxylase 1 (GAD1), vesicular GABA transporter (VGAT), and GABA and the distribution of SST interneurons in the hippocampus through enzyme-linked immunosorbent assay and immunofluorescence. Preoperative 24-h SF exacerbated anesthesia/surgery-induced spatial memory impairments observed in the MWM, NOR, and Y maze tests. Preoperative 24-h SF significantly increased the number of SST interneurons in hippocampal CA1, elevated hippocampal levels of SST, NPY, GAD1, and GABA, and reduced the rCBF. Preoperative SF aggravated POCD in aged male mice, with an increased number of SST interneurons in hippocampal CA1, elevated hippocampal GABAergic metabolites, and a further reduction in rCBF., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Alzheimer's disease (AD) as a neurodegenerative disease can cause behavioral impairments due to oxidative stress. Aging and oxidative conditions are some AD risk factors., Objective: We assessed the influence of geraniol (GR), an acyclic monoterpene alcohol, on behavioral functions, hippocampal oxidative status, and histological alterations in AD rats induced by amyloid-β (Aβ)., Methods: Male Wistar rats (n = 70) were randomly allocated to the control, sham, AD, control-GR (100 mg/kg; per oral: P.O.), AD-GR (100 mg/kg; P.O.; treatment), GR-AD (100 mg/kg; P.O.; pretreatment), and GR-AD-GR (100 mg/kg; P.O.; pretreatment + treatment) groups. GR administration was done for four continuous weeks. After treatments, novel object recognition (NOR) and Morris water maze (MWM) tests assessed the animals' behavior. Then, hippocampal specimens were collected for biochemical assessment. Finally, the number of intact neurons was identified in the hippocampus using hematoxylin and eosin staining., Results: Aβ microinjection increased learning and memory deficits in both NOR and MWM tests, oxidative stress status, and neuronal loss. Oral GR administration improved behavioral deficits and reduced oxidative stress status and neuronal loss in the Aβ-infused animals., Conclusions: GR ameliorates behavioral impairments through a decrease in neuronal degeneration and oxidative stress., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.Alireza Komaki is an Editorial Board Member of this journal but was not involved in the peer-review process of this article nor had access to any information regarding its peer-review.

Objectives: This study investigated the effects of environmental enrichment (EE) on the behavior and histological alterations of rats with barrel cortex damage., Methods: Forty-eight adult male rats were divided into Control (Ctrl), Lesion, Lesion+EE.S (Lesion+Standard Enriched Environment, and Lesion+EE.T (Lesion+Tactile Enriched Environment) groups. The animals were first anesthetized, and then, a cold lesion model was performed on the parietal cortex. After surgery, the rats were exposed to a standard enriched environment or enriched environment with tactile for 30 days. Their cognitive behaviors were assessed using an open field, novel texture discrimination, and Morris water maze (MWM) tests. In addition, a histological investigation was conducted to determine the degree of degeneration of hippocampal and somatosensory cortex neurons., Results: The results demonstrated that rats with barrel cortex lesions revealed impairments in novel texture discrimination and MWM tests (P<0.001). Moreover, lesions increased neuronal degeneration in rats' barrel cortex and hippocampus (P< 0.001). Environmental enrichment improved behavioral deficits and decreased neuronal degeneration in the barrel cortex and hippocampus of rats with barrel cortex lesions (P<0.05)., Conclusion: The current study suggests that barrel cortex lesions create cognitive and behavioral deficits and neural degeneration in the barrel cortex and hippocampus; however, environmental enrichment could reverse these impairments., Competing Interests: Declaration of competing interest The authors declared no potential conflicts with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cognitive dysfunction is the most severe non-motor symptom of Parkinson's disease (PD). Our previous study revealed that hydrogen sulfide (H 2 S) ameliorates cognitive dysfunction in PD, but the underlying mechanisms remain unclear. Hippocampal necroptosis plays a vital role in cognitive dysfunction, while the cGAS/STING pathway triggers necroptosis. To understand the mechanism underlying the inhibitory role of H 2 S in cognitive dysfunction of PD, we explored whether H 2 S reduces the enhancement of necroptosis and the activation of the cGAS/STING pathway in the hippocampus of the rotenone (ROT)-induced PD rat model., Method: Adult Sprague-Dawley (SD) rats were pre-treated with NaHS (30 or 100 μmol/kg/d, i.p.) for 7 days and then co-treated with ROT (2 mg/kg/d, s.i.) for 35 days. The Y-maze and Morris water maze (MWM) tests were used to assess the cognitive function. Hematoxylin-eosin (H&E) staining was used to detect the hippocampal pathological morphology. Western blotting analysis was used to measure the expressions of proteins. Enzyme-linked immunosorbent assay was used to determine the levels of inflammatory factors., Result: NaHS (a donor of H 2 S) mitigated cognitive dysfunction in ROT-exposed rats, according to the Y-maze and MWM tests. NaHS treatment also markedly down-regulated the expressions of necroptosis-related proteins (RIPK1, RIPK3, and MLKL) and decreased the levels of necroptosis-related inflammatory factors (IL-6 and IL-1β) in the hippocampus of ROT-exposed rats. Furthermore, NaHS treatment reduced the expressions of cGAS/STING pathway-related proteins (cGAS, STING, p-TBK1 Ser172 , p-IRF3 Ser396 , and p-P65 Ser536 ) and decreased the contents of pro-inflammation factors (INF-β and TNF-α) in the hippocampus of ROT-exposed rats., Conclusion: H 2 S attenuates the cGAS/STING pathway-triggered necroptosis in the hippocampus, which is related to H 2 S to attenuate cognitive dysfunction in PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Brain iron overload may induce neuronal death and lead to cognitive impairment. The hippocampus is a critical limbic structure involved in memory. This study aimed to investigate iron overload and its role in hippocampal damage and memory impairment using a rat model., Methods: Young rats (2 weeks old) received intraperitoneal injections of high-dose iron solution (Group H, n = 10), low-dose iron solution (Group L, n = 10) and normal saline as control (Group D, n = 5). The Morris water maze (MWM) test was performed on all rats to evaluate their spatial reference memory by assessing their escape latency time and number of platform crossing. The iron content and neuronal damage in hippocampal tissue sections of the rats were assessed semi-quantitatively using diaminobenzidine (DAB)-enhanced Perl's Prussian blue (PPB) staining, and their correlation with spatial reference memory performance was evaluated., Results: The escape latency in Group H was significantly longer compared to Groups L and D (P < 0.05). The number of platform crossings was significantly lower in Group H than in Group L or D (P < 0.001). The neuronal cells in Group H had more brown iron deposits than those of Groups L and D. There were significant correlations between the severity of structural damage in the hippocampal tissue and the number of platform crossings (P 1  = 0.001 for Group H; P 2  = 0.043 for Group L)., Conclusion: This study showed an association between hippocampal iron-induced structural damage and spatial reference memory impairment in a rat model. This work should advance our understanding of hippocampal iron overload on cognitive functioning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aims to investigate whether glial cells, in particular putative astrocytes, contribute to functional distinctions between the dorsal (DH), intermediate (IH), and ventral (VH) hippocampus. To evaluate this, we performed three different behavioral tasks (i.e., Morris water maze; MWM, Passive avoidance; PA, T-maze place preference; TPP) to determine whether the DH, IH, and VH are necessary for each task. Sensitivity of behavioral tasks was confirmed using lidocaine (2 %, 1 μl) reversible inactivation. Subsequently, we examined the effects of silencing astrocytes, using fluorocitrate (FC, 1 mM/1 μl), into the DH, IH, and VH on these tasks. The effects of drugs were examined separately. We observed that injection of FC into the DH resulted in a significant impairment in MWM performance. In contrast, while FC injections into the IH or VH did not prevent platform localization during the acquisition phase, rats showed difficulty recalling the target zone during the retrieval phase. In the PA test, FC injection into the VH impaired task learning and memory. During the acquisition phase, FC injection into the DH or IH did not differ from the control in the number of shocks; however, during retrieval, there was a significant decrease in the latency before entering the dark chamber. The TPP test performance was impaired by FC injection in the IH. In sum, we show that glial cells, especially astrocytes in specific functional regions of the hippocampus, play distinct roles in processing aversive and rewarding experiences and contribute to the functional organization of the hippocampal longitudinal axis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Background: Noise pollution pervades daily working and living environment, becoming a serious public health problem. In addition to causing auditory impairment, noise independently contributes to cognitive decline as a risk factor. Though neuroinflammation plays an important role in noise-induced cognitive deficits, the mechanisms underlying noise-induced neuroinflammation in the hippocampus are still poorly understood. Glial hyperactivation of the NLRP3 inflammasome contributes to various neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). However, whether the NLRP3 inflammasome plays a role in noise-induced cognitive impairment remains to be further investigated., Methods: Adult male Wistar rats were exposed to 100 dB white noise (4 h/day) for 30 days with or without injection of the NLRP3 inhibitor MCC950 (10 mg/kg/day). The Morris water maze (MWM) test and the open field test (OFT) were performed to evaluate learning and memory ability of rats. HE staining was used to explore hippocampal pathological changes, while immunohistochemical staining was employed to evaluate the number and morphology of microglia and astrocytes. The mRNA levels of the NLRP3 inflammasome in the hippocampus were examined by Real-time PCR. The protein levels of NLRP3 inflammasome, inflammatory cytokines, p-Tau-S396, and amyloid-β (Aβ) 42 in the hippocampus were examined by Western blot. Immunofluorescence was used to observe the distribution of NLRP3 in glial cells and neurons, and the assembly of the NLRP3 inflammasome., Results: We found that noise exposure induced learning and memory impairment in rats, mainly related to the activation of microglia and astrocytes in hippocampus region. Noise exposure increased the protein levels of p-Tau-S396, Aβ42, ionized calcium binding adapter molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), interleukin (IL)-1β, IL-18, and tumor necrosis factor-α (TNF-α) in hippocampus. Furthermore, the hippocampus of noise-exposed rats showed elevated protein levels of NLRP3, ASC and cleaved caspase-1. The co-labeled immunofluorescence levels of Iba-1 or GFAP with NLRP3 significantly increased in the dentate gyrus (DG) region of the hippocampus. NLRP3 inhibitor MCC950 intervention reversed chronic noise-induced activation of NLRP3 inflammasome, AD-like pathologies and impairment of learning and memory in rats., Conclusions: The NLRP3 inflammasome-mediated neuroinflammation played an essential role in chronic noise-induced cognitive dysfunction. These results provide novel strategies for the prevention and treatment of cognitive deficits caused by chronic noise., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: It is well established that glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies indicate that glutamate dynamics shift with Alzheimer's disease (AD) progression, contributing to negative cognitive outcomes., Objective: In this study, we characterized hippocampal glutamatergic signaling with age and disease progression in a knock-in mouse model of AD (APP NL-F/NL--F )., Methods: At 2-4 and 18+ months old, male and female APP NL/NL , APP NL-F/NL-F , and C57BL/6 mice underwent cognitive assessment using Morris water maze (MWM) and Novel Object Recognition (NOR). Then, basal and 70 mM KCl stimulus-evoked glutamate release was measured in the dentate gyrus (DG), CA3, and CA1 regions of the hippocampus using a glutamate-selective microelectrode in anesthetized mice., Results: Glutamate recordings support elevated stimulus-evoked glutamate release in the DG and CA3 of young APP NL-F/NL-F male mice that declined with age compared to age-matched control mice. Young female APP NL-F/NL-F mice exhibited increased glutamate clearance in the CA1 that slowed with age compared to age-matched control mice. Male and female APP NL-F/NL-F mice exhibited decreased CA1 basal glutamate levels, while males also showed depletion in the CA3. Cognitive assessment demonstrated impaired spatial cognition in aged male and female APP NL-F/NL-F mice, but only aged females displayed recognition memory deficits compared to age-matched control mice., Conclusions: These findings confirm a sex-dependent hyper-to-hypoactivation glutamatergic paradigm in APP NL-F/NL-F mice. Further, data illustrate a sexually dimorphic biological aging process resulting in a more severe cognitive phenotype for female APP NL-F/NL-F mice than their male counterparts. Research outcomes mirror that of human AD pathology and provide further evidence of divergent AD pathogenesis between sexes., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

It is known that exercise increases brain-derived neurotrophic factor (BDNF) levels in the hippocampus, the brain region responsible for learning and memory, resulting in improved cognitive functions and learning processes. However, it is claimed that different types of exercise cause different responses in the brain. It is thought that lactate and osteocalcin secreted in response to exercise are associated with an increase in BDNF levels. However, there are not enough studies on this subject. This study aimed to compare the effects of high-intensity interval training (HIIT) and voluntary exercise training on cognitive performance and molecular connections. Male rats were randomly divided into control, voluntary exercise training and HIIT groups. The voluntary exercise group had free access to the voluntary wheel for 8 weeks. The HIIT group performed HIIT on the treadmill 3 days a week for 8 weeks. The rats underwent open field (OF), elevated plus maze (EPM) and Morris water maze (MWM) tests 24 h after the last exercise training. Then, after blood was drawn under anesthesia, the rats were sacrificed and their hippocampus tissues were separated. Glucocorticoid and BDNF levels in the blood were evaluated by enzyme-linked immunosorbent assay (ELISA), and osteocalcin and BDNF expressions in the hippocampus were evaluated by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Neither voluntary exercise training nor HIIT had any significant effect on behavioral parameters assessed by OF, EPM and MWM tests. However, BDNF expression in hippocampus tissue was higher in the HIIT group than in the control group. In addition, osteocalcin expression in hippocampus tissue was higher in the HIIT and voluntary exercise groups than in the control group. In conclusion, according to the findings we obtained from this study, although it does not have a significant effect on cognitive functions, the effect of HIIT on brain functions seems to be more effective than voluntary exercise., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterised by cognitive dysfunction, memory loss and mood changes. Hippocampal neurogenesis has been suggested to play a role in learning and memory. Neurokinin 3 receptor (NK3R) has been shown to be prevalent in the hippocampus region. The aim of the project was to investigate the role of hippocampal neurogenesis in the promnestic effects of NK3R agonist administration in an amyloid beta-induced AD rat model. Wistar albino rats were divided into control, Alzheimer, NK3R agonist and Alzheimer + NK3R agonist groups. The open field (OF) test and Morris water maze (MWM) test were performed for locomotor activity and memory analysis. Peptide gene expression levels (Nestin, DCX, Neuritin, MASH1, Neun, BDNF) were analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR). In the OF test, the group-time relationship was found to be statistically different in the parameters of distance travelled and percentage of movement (p < 0.05). In MWM, the time to reach the platform and the time spent in the target quadrant were statistically significant between the groups (p < 0.05). Statistically significant differences were observed in gene expression levels (Nestin, DCX, Neuritin, MASH1) in the hippocampal tissue of rats between the groups (p < 0.05). NK3 receptor agonism favourably affected hippocampal neurogenesis in AD model rats. It was concluded that NK3 receptor agonism in the hippocampus, which is the first affected region in the physiopathology of AD, may be effective in both the formation of neural precursor cells and the reduction of neuronal degeneration. The positive effect of NK3R on cognitive functions may be mediated by hippocampal neurogenesis., (© 2024 International Society for Developmental Neuroscience.)

Background: The molecular biology mechanisms underlying postoperative cognitive dysfunction (POCD) remain unclear, resulting in a lack of specific therapeutic targets and limited clinical treatment options. The NLRP3 pyroptotic pathway, induced by neuroinflammation, is known to promote the development of POCD. Research has shown that lncRNA MEG3 exacerbates cell pyroptosis in various neurological injuries, though the precise mechanism remains to be investigated., Methods: In vitro and in vivo models of POCD were established through treatment with sevoflurane. Gene and protein expression were investigated using qRT-PCR, Western blot analysis, ELISA, and histological staining. Additionally, cell viability and injury were assessed through CCK-8 and LDH assays. Hippocampal-dependent memory and cognitive abilities were evaluated using the Morris Water Maze (MWM) test. Furthermore, the interactions between MEG3 and EZH2/YTHDC1 were validated through RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP)., Results: Our findings reveal that sevoflurane significantly reduced MEG3 and pyroptosis-related proteins in mice. The overexpression of MEG3 protected mice against sevoflurane-induced cognitive dysfunction and reversed sevoflurane-induced pyroptosis in hippocampal neurons. MEG3 induced the downregulation of NLRP3 expression and reduced mRNA stability through its interaction with EZH2/YTHDC1., Conclusion: In conclusion, our study elucidates that MEG3 inhibits the NLRP3 inflammasome and hippocampal neuron pyroptosis through the recruitment of EZH2/YTHDC1. These findings shed light on the underlying mechanism of MEG3 in the regulation of POCD and suggest that MEG3 could serve as a potential therapeutic target for the treatment of POCD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chronic stress can induce the cognitive impairment, and even promote the occurrence and development of Alzheimer's disease (AD). Evidence has suggested that chronic stress impacts on glucose metabolism, and both of these have been implicated in AD. Here we focused on the effect of insulin resistance in glucose metabolism, and further evaluated the changes in cognition and pathology., Methods: Male 9-month-old wild-type and APP/PS1 mice were randomly divided into 4 groups. Mice in the chronic unpredictable mild stress (CUMS) groups were exposed for 4 weeks. Homeostatic Model Assessment (HOMA) was utilized to evaluate insulin sensitivity. A total of eighty-four genes related to the insulin signaling pathway were examined for rapid screening. Additionally, the phosphorylated protein expressions of insulin receptors (IR), IR substrate 1 (IRS1), c-Jun N-terminal kinase (JNK), and amyloid were detected in the hippocampus. Cognitive function was assessed through ethological methods. Cognitive function was assessed using both the Morris water maze (MWM) and the Passive avoidance test (PAT)., Results: Four weeks of CUMS exposure significantly increased the HOMA value, indicating reduced insulin sensitivity. The gene expressions of Insr and Lipe were downregulated. Additionally, the analysis revealed a significant interaction between the genotype (wild-type vs. APP/PS1) and CUMS treatment on the phosphorylated protein expressions of insulin receptor substrate 1 (IRS1). Specifically, CUMS exposure increased the inhibitory phosphorylation site (IRS1-pSer636) and decreased the excitatory phosphorylation site (IRS1-pTyr465) in the post-insulin receptor signaling pathway within the hippocampus of both wild-type and APP/PS1 mice. Moreover, CUMS exposure induced and exacerbated cognitive impairments in both wild-type and APP/PS1 mice, as assessed by the Morris water maze (MWM) and Passive avoidance test (PAT). However, there was no significant effect of CUMS on senile plaque deposition or levels of Aβ42 and Aβ40 in wild-type mice., Conclusions: Chronic stress significantly affects hippocampal cognitive function through insulin resistance and exacerbates AD pathology. This study reveals the complex relationship between chronic stress, insulin resistance, and AD, providing new insights for developing interventions targeting chronic stress and insulin resistance., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic stress leads to social avoidance and anhedonia in susceptible individuals, a phenomenon that has been observed in both human and animal models. Nevertheless, the underlying molecular mechanisms underpinning stress susceptibility and resilience remain largely unclear. There is growing evidence that epigenetic histone deacetylase (HDAC) mediated histone acetylation is involved in the modulation of depressive-related behaviors. We hypothesized that histone deacetylase 5 (HDAC5), which is associated with stress-related behaviors and antidepressant response, may play a vital role in the susceptibility to chronic stress. In the current study, we detected the levels of HDAC5 and acetylation of histone 4 (H4) in the hippocampus subsequent to chronic social defeat stress (CSDS) in C57BL/6J mice. We found that CSDS induces a notable increase in HDAC5 expression, concomitant with a reduction in the acetylation of histone H4 at lysine 12 (H4K12) in the hippocampus of susceptible mice. Meanwhile, intrahippocampal infusion of HDAC5 shRNA or HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) both reversed the depression susceptibility in susceptible mice that subjected to CSDS. Furthermore, HDAC5 overexpression was sufficient to induce depression susceptibility following microdefeat stress, accompanied by a significant reduction in H4K12 level within the hippocampus of mice. Additionally, the Morris water maze (MWM) results indicated that neither CSDS nor HDAC5 exerted significant effects on spatial memory function in mice. Taken together, these investigations indicated that HDAC5-modulated histone acetylation is implicated in regulating the depression susceptibility, and may be serve as potential preventive targets for susceptible individuals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Unhealthy lifestyles, such as chronic consumption of a Western Diet (WD), have been associated with increased systemic inflammation and oxidative stress (OS), a condition that may favour cognitive dysfunctions during aging. Polyphenols, such as rosmarinic acid (RA) may buffer low-grade inflammation and OS, characterizing the aging brain that is sustained by WD, promoting healthspan. The aim of this study was to evaluate the ability of RA to prevent cognitive decline in a mouse model of WD-driven unhealthy aging and to gain knowledge on the specific molecular pathways modulated within the brain., Methods: Aged male and female C57Bl/6N mice were supplemented either with RA or vehicle for 6 weeks. Following 2 weeks on RA they started being administered either with WD or control diet (CD). Successively all mice were tested for cognitive abilities in the Morris water maze (MWM) and emotionality in the elevated plus maze (EPM). Glucose and lipid homeostasis were assessed in trunk blood while the hippocampus was dissected out for RNAseq transcriptomic analysis., Results: RA prevented insulin resistance in males while protecting both males and females from WD-dependent memory impairment. In the hippocampus, RA modulated OS pathways in males and immune- and sex hormones-related signalling cascades (Lhb and Lhcgr genes) in females. Moreover, RA overall resulted in an upregulation of Glp1r, recently identified as a promising target to prevent metabolic derangements. In addition, we also found an RA-dependent enrichment in nuclear transcription factors, such as NF-κB, GR and STAT3, that have been recently suggested to promote healthspan and longevity by modulating inflammatory and cell survival pathways., Conclusions: Oral RA supplementation may promote brain and metabolic plasticity during aging through antioxidant and immune-modulating properties possibly affecting the post-reproductive hormonal milieu in a sex-dependent fashion. Thus, its supplementation should be considered in the context of precision medicine as a possible strategy to preserve cognitive functions and to counteract metabolic derangements., Competing Interests: Conflict of interest K.S. was employed by AnalytiCon Discovery GmbH, Potsdam, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All authors have approved the manuscript in its final form., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hypoxia in preterm infants is a clinical condition that has been associated with cognitive and behavioral disturbances for which treatment strategies are strongly required. Melatonin administration following brain insults has been considered a promising therapeutic strategy due to its antioxidant and anti-inflammatory effects. Not surprisingly, it has been extensively studied for preventing disturbances following brain injury. This study evaluated the effects of melatonin on developmental disturbances, memory disruption, and hippocampal cell loss induced by neonatal anoxia in rats. Neonatal Wistar rats were subjected to anoxia and subsequently treated with melatonin. Later, maturation of physical characteristics, ontogeny of reflexes, learning and memory in the Morris water maze (MWM), and estimates of the number of hippocampal neurons, were evaluated. Melatonin treatment attenuated (1) female anoxia-induced delay in superior incisor eruption, (2) female anoxia-induced vibrissae placement reflexes, and (3) male and female anoxia-induced hippocampal neuronal loss. Melatonin also promoted an increase (5) in swimming speeds in the MWM. In addition, PCA analysis showed positive associations between the acoustic startle, auditory canal open, and free fall righting parameters and negative associations between the male vehicle anoxia group and the male melatonin anoxia group. Therefore, melatonin treatment attenuates both anoxia-induced developmental deficits and hippocampal neuronal loss., (© 2024 International Society for Developmental Neuroscience.)

Introduction: Whether repeated inhalation of sevoflurane during the neonatal period causes long-term learning and memory impairments in humans is unclear. Some recent investigations have indicated that general anesthesia drugs affect histone methylation modification and may further affect learning and memory ability. This study aimed to explore the role and mechanism of histone methylation in long-term cognitive dysfunction caused by repeated inhalation of sevoflurane during the neonatal period. Methods: Neonatal SD rats were assigned into three groups. Sevoflurane group and sevoflurane +AS8351 group were exposed to 2% sevoflurane for 4 h on postnatal day 7 (P7), day 14 (P7) and day 21 (P21), and the control group was inhaled the air oxygen mixture at the same time. From postnatal day 22 to 36, rats in the +AS8351 group were treated with AS8351 while those in the Sevoflurane group and control group were treated with normal saline. Half of the rats were carried out Y-maze, Morris water maze (MWM), western blot and transmission electron microscope at P37, and the remaining rats were fed to P97 for the same experiment. Results: Neonatal sevoflurane exposure affected histone demethylase expression in hippocampus, changed histone methylation levels, Down-regulated synapse-associated protein expression, impaired synaptic plasticity and long-term cognitive dysfunction and KDM5B inhibitors partially restored the negative reaction caused by sevoflurane exposure. Discussion: In conclusion, KDM5B inhibitor can save the long-term learning and memory impairment caused by sevoflurane exposure in neonatal period by inhibiting KDM5B activity. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia and progressive cognitive dysfunction, and our clinical investigation revealed that the plasma concentration of melatonin (Mlt) decreased and was closely related to cognition in T2DM patients. However, although many studies have suggested that Mlt has a certain protective effect on glucose and lipid metabolism disorders and neuropsychiatric injury, the underlying mechanism of Mlt against T2DM-related metabolic and cognitive impairments remains unclear., Purpose: The aim of the present study was to investigate the therapeutic effect of Mlt on metabolic disorders and Alzheimer's disease (AD)-like neuropsychiatric injuries in T2DM mice and to explore the possible underlying molecular mechanism involved., Methods: A T2DM mouse model was established by a combination of a high-fat diet (HFD) and streptozotocin (STZ, 100 mg/kg, i.p.), and Mlt (5, 10 or 20 mg/kg) was intragastrically administered for six consecutive weeks. The serum levels of glycolipid metabolism indicators were measured, behavioral performance was tested, and the protein expression of key molecules involved in the regulation of synaptic plasticity, circadian rhythms, and neuroinflammation in the hippocampus was detected. Moreover, the fluorescence intensities of glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule 1 (IBA-1), amyloid β-protein (Aβ) and phosphorylated Tau (p-Tau) in the hippocampus were also observed., Results: Treatment with Mlt not only improved T2DM-related metabolic disorders, as indicated by increased serum concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbAlc), insulin (INS), total cholesterol (TC) and triglyceride (TG), improved glucose tolerance and liver and pancreas function but also alleviated AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, as indicated by decreased immobility time in the tail suspension test (TST) and forced swimming test (FST), increased preference indices of novel objects or novel arms in the novel object recognition test (NOR) and Y-maze test (Y-maze), and improved platform positioning capability in the Morris water maze (MWM) test. Moreover, treatment with Mlt also improved the hyperactivation of astrocytes and microglia in the hippocampus of mice, accompanied by reduced expression of interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), Aβ, and p-Tau and increased expression of brain-derived neurotrophic factor (BDNF), Synapsin I, Synaptotagmin I, melatonin receptor 1B (MT1B), brain muscle arnt-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), period 2 (Per2), and cryptochrome 2 (Cry2)., Conclusion: Mlt alleviated T2DM-related metabolic disorders and AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, possibly through a mechanism involving the regulation of glial activation and associated neuroinflammation and the balancing of synaptic plasticity and circadian rhythms in the hippocampus., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The persistence of the novel brominated flame retardant, bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (TBPH), in the environment and its potential for bioaccumulation in living organisms, including humans, further exacerbate its health risks. Therefore, ongoing research is crucial for fully understanding the extent of TBPH's neurotoxicity and for developing effective mitigation strategies. This study aims to investigate the potential neurotoxicity of TBPH on mouse neurobehavior and to evaluate the protective effects of the natural antioxidant astaxanthin (AST) against TBPH-induced neurotoxicity. The results indicate that exposure to TBPH can lead to a decline in learning and memory abilities and abnormal behaviors in mice, which may be associated with oxidative stress responses and apoptosis in the hippocampus. TBPH may disrupt the normal function of hippocampal neurons by activating the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Mice exposed to TBPH treated with AST showed improved learning and memory abilities in the Morris water maze (MWM) and Step-down test (SDT). AST, through its antioxidant action, was able to significantly reduce the increase in reactive oxygen species (ROS) levels induced by TBPH, the increased expression of apoptosis markers, and the activation of the ERK1/2-FOS signaling pathway, alleviating TBPH-induced apoptosis in hippocampal neurons and improving neurobehavioral outcomes. These findings suggest that AST may alleviate the neurotoxicity of TBPH by modulating molecular events related to apoptosis and the ERK1/2-FOS signaling pathway. Thus, this study provides evidence for AST as a potential interventional strategy for the prevention or treatment of cognitive decline associated with environmental neurotoxicant exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to compare the effects of High-Intensity Interval Training (HIIT) performed in a single session(1xHIIT) versus three daily sessions (3xHIIT) on fitness level and behavior of aged rats. Eighteen-month-old Wistar rats were assigned to Untrained (UN), 1xHIIT, or 3xHIIT (n = 12/group). Both groups, 1xHIIT and 3xHIIT, performed 15 min of a treadmill running HIIT protocol during 8 weeks. 1xHIIT protocol consisted of a single daily session of 15 min, while the 3xHIIT performed three daily sessions of 5 min with a 4 h interval between the sessions. Morris Water Maze (MWM) task was used to evaluate spatial learning and memory. Splash test, Forced Swim test, and Elevated Plus Maze task (EPM) were used to evaluate anhedonic, depressive-like, and anxious behaviors, respectively. Rats were euthanized, and the hippocampus was harvested for western blot analyses (CaMKII and BDNF). Both HIIT protocols improved VO 2 max and spatial memory. Notably, only the 3xHIIT protocol attenuated anxious and depressive-like behaviors. Western blot analyses of the hippocampus revealed that both HIIT protocols increased BDNF levels. BDNF levels were higher in the 3xHIIT when compared with 1xHIIT group, and we observed increasement of the CamKII levels just in the 3x HIIT group. Therefore, this study provides evidence indicating that accumulated HIIT sessions is more effective than traditional daily HIIT sessions in improving fitness level, cognitive function, memory, inhibiting the development of mood disorders, and enhancing BDNF and CaMKII levels in the hippocampus of aged rats., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore the mechanism by which Tongqiao Yizhi granule (, TQYZKL) intervenes pyroptosis to treat vascular dementia (VaD) in a rat model., Methods: The rat model of VaD was established by two-vessel occlusion (2VO). The rats were randomly divided into Sham group, Model group, Nimodipine group, TQYZKL (6.2 g?kg -1 ?d -1 ), TQYZKL (12.4 g?kg -1 ?d -1 ), TQYZKL (24.8 g?kg -1 ?d -1 ). The Morris water maze (MWM) test was carried out to test the learning and memory function; Hematoxylin-eosin staining and transmission electron microscopy (TEM) to observe the pathological damage in the hippocampus; Tunel fluorescence staining to detect neuronal pyroptosis in the hippocampus. The expression levels of pyroptosis-related proteins, namely Golgi peripheral membrane protein p65 (P65), nucleotide oligomerization domain-like receptors 3 (NLRP3), caspase-1 and Gasdermin D (GSDMD), were detected using Western blotting and reverse transcription polymerase chain reaction. Moreover, the serum levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were determined through the enzyme-linked immunosorbent assay., Results: The study revealed that TQYZKL effectively improved the ability of VaD ratsto learn and memorize, relieved the pathological damage in the hippocampus, restored neuronal morphology, and reduced the expression of pyroptosis-related proteins P65, NLRP3, caspase-1, GSDMD-N, IL-18 and IL-1β ( P < 0.05)., Conclusion: TQYZKL inhibits neuronal pyroptosis in the hippocampus of VaD rats by regulating nuclear factor kappa-B/NLRP3/caspase-1 signaling pathway, thus exerting a therapeutic effect on VaD in the rats.

Vitamin D deficiency (VDD) is widespread around the world and has been extensively documented to affect various health conditions, including the cognitive functioning of the brain. Serum 25-hydroxylated forms of vitamin D are traditionally used to determine vitamin D status. However, there is now evidence that cholecalciferol activation can occur and be controlled by locally expressed enzymes in the brain. This study aimed to investigate the effects of cholecalciferol supplementation on cognitive function in rats who underwent transient VDD in adulthood. Thirty-six adult Wistar rats were administered paricalcitol (seven doses of 32 ng injected every other day) along with a "vitamin D-free" diet to induce VDD, which was confirmed using a LC-MS/MS serum analysis of the cholecalciferol and 25-hydroxyvitamin D3 levels. Treatment was performed by including 1000 IU/kg and 10,000 IU/kg cholecalciferol in the diet. Cognitive performance was evaluated using the novel object recognition (NOR), Morris water maze (MWM), and radial arm maze (RAM) tests. An immunohistochemical analysis of the brain regions involved in learning and memory was performed by quantifying the neurons, astrocytes, and microglia labelled with anti-neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1) antibodies, respectively. The vitamin D deficient group showed the lowest performance in both the MWM and RAM tests. In contrast, the cholecalciferol-treated groups exhibited a faster learning curve. However, no difference was detected between the groups in the NOR test. On the other hand, differences in the cellular organization of the hippocampus and amygdala were observed between the groups. Cholecalciferol supplementation decreased the density of the Iba-1- and GFAP-labeled cells in the hilus and cornu Ammonis 3 (CA3) regions of the hippocampus and in the amygdala. These results support vitamin D's substantial role in learning and memory. They also highlight that subtle changes of cognitive function induced by transient VDD could be reversed by cholecalciferol supplementation. Further studies are needed to better understand VDD and cholecalciferol's effects on the brain structure and function.

The present study was conducted to investigate the effects of Ocimum basilicum L. (OB) extract on learning and memory impairment in aged rats. Male rats were divided into the following experimental groups: Group 1 (control): including 2 months old rats, Group 2 (aged) including 2 years old rats, Groups 3-5 (aged-OB): including 2 years old rats received 50, 100, and 150 mg/kg OB for 8 weeks by oral gavage. Aging increased the delay to find the platform but, however, decreased the time spent in the target quadrant when tested by Morris water maze (MWM). Aging also reduced the latency to enter the dark chamber in the passive avoidance (PA) test compared to the control group. Moreover, interleukin-6 (IL-6) and malondialdehyde (MDA) levels were raised in the hippocampus and cortex of aged rats. In contrast, thiol levels and enzymatic activity of superoxide dismutase (SOD) and catalase (CAT) significantly reduced. In addition, aging significantly reduced BDNF expression. Finally, OB administration reversed the mentioned effects. The current research showed that OB administration improves learning/memory impairment induced by aging. It also found that this plant extract protects the brain tissues from oxidative damage and neuroinflammation.

Depression frequently occurs following traumatic brain injury (TBI). However, the role of Fibromodulin (FMOD) in TBI-related depression is not yet clear. Previous studies have suggested FMOD as a potential key factor in TBI, yet its association with depression post-TBI and underlying mechanisms are not well understood. Serum levels of FMOD were measured in patients with traumatic brain injury using qPCR. The severity of depression was assessed using the self-depression scale (SDS). Neurological function, depressive state, and cognitive function in mice were assessed using the modified Neurological Severity Score (mNSS), forced swimming test (FST), tail suspension test (TST), Sucrose Preference Test (SPT), and morris water maze (MWM). The morphological features of mouse hippocampal synapses and neuronal dendritic spines were revealed through immunofluorescence, transmission electron microscopy, and Golgi-Cox staining. The protein expression levels of FMOD, MAP2, SYP, and PSD95, as well as the phosphorylation levels of the PI3K/AKT/mTOR signaling pathway, were detected through Western blotting. FMOD levels were decreased in TBI patients' serum. Overexpression of FMOD preserved neuronal function and alleviated depression-like behaviour, increased synaptic protein expression, and induced ultrastructural changes in hippocampal neurons. The increased phosphorylation of PI3K, AKT, and mTOR suggested the involvement of the PI3K/AKT/mTOR signaling pathway in FMOD's protective effects. FMOD exhibits potential as a therapeutic target for depression related to TBI, with its protective effects potentially mediated through the PI3K/AKT/mTOR signaling pathway., (© 2024. The Author(s).)

Poststroke cognitive impairment (PSCI) is a common complication of stroke, but effective treatments are currently lacking. Repetitive transcranial magnetic stimulation (rTMS) is gradually being applied to treat PSCI, but there is limited evidence of its efficacy. To determine rTMS effects on PSCI, we constructed a transient middle cerebral artery occlusion (tMCAO) rat model. Rats were then grouped by random digital table method: the sham group (n = 10), tMCAO group (n = 10) and rTMS group (n = 10). The shuttle box and Morris water maze (MWM) tests were conducted to detect the cognitive functions of the rats. In addition, synaptic density and synaptic ultrastructural parameters, including the active zone length, synaptic cleft width, and postsynaptic density (PSD) thickness, were quantified and analyzed using an electron microscope. What's more, synaptic associated proteins, including PSD95, SYN, and BDNF were detected by western blot. According to the shuttle box and MWM tests, rTMS improved tMCAO rats' cognitive functions, including spatial learning and memory and decision-making abilities. Electron microscopy revealed that rTMS significantly increased the synaptic density, synaptic active zone length and PSD thickness and decreased the synaptic cleft width. The western blot results showed that the expression of PSD95, SYN, and BDNF was markedly increased after rTMS stimulation. Based on these results, we propose that 20 Hz rTMS can significantly alleviate cognitive impairment after stroke. The underlying mechanism might be modulating the synaptic plasticity and up-regulating the expression PSD95, SYN, and BDNF in the hippocampus., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Electroconvulsive shock (ECS) is utilized to treat depression but may cause learning/memory impairments, which may be ameliorated by anesthetics through the modulation of hippocampal synaptic plasticity. Given that synaptic plasticity is governed by aerobic glycolysis, it remains unclear whether anesthetics modulate aerobic glycolysis to enhance learning and memory function. Depression-like behavior in rats was induced by chronic mild unpredictable stress (CUMS), with anhedonia assessed via sucrose preference test (SPT). Depressive-like behaviors and spatial learning/memory were assessed with forced swim test (FST), open field test (OFT), and Morris water maze (MWM) test. Changes in aerobic glycolysis and synaptic plasticity in the hippocampal region of depressive-like rats post-ECS were documented using immunofluorescence analysis, Western blot, Lactate Assay Kit and transmission electron microscopy. Both the OFT and FST indicated that ECS was effective in alleviating depressive-like behaviors. The MWM test demonstrated that anesthetics were capable of attenuating ECS-induced learning and memory deficits. Immunofluorescence analysis, Western blot, Lactate Assay Kit and transmission electron microscopy revealed that the decline in learning and memory abilities in ECS-induced depressive-like rats was correlated with decreased aerobic glycolysis, and that the additional use of ciprofol or propofol ameliorated these alterations. Adding the glycolysis inhibitor 2-DG diminished the ameliorative effects of the anesthetic. No significant difference was observed between ciprofol and propofol in enhancing aerobic glycolysis in astrocytes and synaptic plasticity after ECS. These findings may contribute to understanding the mechanisms by which anesthetic drugs modulate learning and memory impairment after ECS in depressive-like behavior rats., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The Rabies virus is a neurotropic virus that manipulates the natural cell death processes of its host to ensure its own survival and replication. Studies have shown that the anti-apoptotic effect of the virus is mediated by one of its protein named, rabies glycoprotein (RVG). Alzheimer's disease (AD) is characterized by the loss of neural cells and memory impairment. We aim to examine whether expression of RVG in the hippocampal cells can shield the detrimental effects induced by Aβ. Oligomeric form of Aβ (oAβ) or vehicle was bilaterally microinjected into the dorsal hippocampus of male Wistar rats. One week later, two μl (10 8 T.U. /ml) of the lentiviral vector carrying RVG gene was injected into their dorsal hippocampus (post-treatment). In another experiment, the lentiviral vector was microinjected one week before Aβ injection (pre-treatment). One week later, the rat's brain was sliced into cross-sections, and the presence of RVG-expressing neuronal cells was confirmed using fluorescent microscopy. Rats were subjected to assessments of spatial learning and memory as well as passive avoidance using the Morris water maze (MWM) and the Shuttle box apparatuses, respectively. Protein expression of AMPA receptor subunit (GluA1) was determined using western blotting technique. In MWM, Aβ treated rats showed decelerated acquisition of the task and impairment of reference memory. RVG expression in the hippocampus prevented and restored the deficits in both pre- and post- treatment conditions, respectively. It also improved inhibitory memory in the oAβ treated rats. RVG increased the expression level of GluA1 level in the hippocampus. Based on our findings, the expression of RVG in the hippocampus has the potential to enhance both inhibitory and spatial learning abilities, ultimately improving memory performance in an AD rat model. This beneficial effect is likely attributed, at least in part, to the increased expression of GluA1-containing AMPA receptors., (© 2024. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)

Recent studies have found that gut microbes may affect blood-brain barrier (BBB) integrity. This study was to investigate the relationship between gut microbes and forkhead box F2 (FOXF2) and the mechanism of troxerutin improving diabetic cognitive dysfunction (DCD). Diabetic mice were used in this study for the prophylactic application of troxerutin (60 mg/kg/d) for 8 weeks. The cognitive function was assessed using the Morris water maze (MWM) and novel object recognition (NOR) tasks, and the changes of intestinal microbial composition were observed through 16S rRNA gene sequencing. The content of short-chain fatty acids (SCFAs) in feces was determined by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the intestinal barrier function was assessed by enzyme-linked immunosorbent assay (ELISA) and western blotting. Troxerutin up-regulated FOXF2 expression in the hippocampus of mice, improving DCD. Meanwhile, it reversed the intestinal microbial composition (increased the abundance of the phylum Bacteroidota, as well as fecal propionic acid and butyric acid levels) and improved the intestinal barrier (increased the level of claudin-1 and significantly reduced the circulating lipopolysaccharide binding protein (LBP) levels). When intestinal microorganisms were removed with an antibiotic cocktail, the improvement of hippocampal FOXF2 expression and DCD by troxerutin attenuated accordingly, suggesting that troxerutin improved DCD by up-regulating the expression of hippocampal FOXF2 through the regulation of intestinal microbial composition and the intestinal barrier. In summary, troxerutin improved DCD by up-regulating the expression of hippocampal FOXF2 through the regulation of intestinal microbial composition and the intestinal barrier., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Tooth loss is closely related to cognitive impairment, especially affecting cognitive functions involving hippocampus. The most well-known function of the hippocampus is learning and memory, and the mechanism behind is neuroplasticity, which strongly depends on the level of brain-derived neurotrophic factor (BDNF). While research has delved into the possible mechanisms behind the loss of teeth leading to cognitive dysfunction, there are few studies on the plasticity of sensory neural pathway after tooth loss, and the changes in related indicators of synaptic plasticity still need to be further explored., Methods: In this study, the bilateral maxillary molars were extracted in Sprague-Dawley rats of two age ranges (young and middle age) to establish occlusal support loss model; then, the spatial cognition was tested by Morris Water Maze (MWM). Quantitative real-time PCR (qPCR) and Western Blotting (WB) were used to detect BDNF, AKT, and functional proteins (viz., PSD95 and NMDAR) of hippocampal synapses. Golgi staining was used to observe changes in ascending nerve pathway. IF was used to confirm the location of BDNF and AKT expressed in hippocampus., Results: MWM showed that the spatial cognitive level of rats dropped after occlusal support loss. qPCR, WB, and IF suggested that the BDNF/AKT pathway was down-regulated in the hippocampus. Golgi staining showed the neurons of ascending sensory pathway decreased in numbers., Conclusion: Occlusal support loss caused plastic changes in ascending nerve pathway and induced cognitive impairment in rats by down-regulating BDNF and synaptic plasticity., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Cognitive dysfunction (CD) is a neurodegenerative disease characterized primarily by the decline of learning and memory abilities. The physiological and pathological mechanisms of CD are very complex, which is mainly related to normal function of the hippocampus. Lancao decoction (LC) is a Chinese medicine formula, which has been used to treat neurodegenerative disorders. However, the potential of LC for the treatment of CD, as well as its underlying mechanisms, is unclear., Purpose: In the study, we aimed to reveal the functional and neuronal mechanisms of LC's treatments for CD in scopolamine-induced mice., Methods: Gas chromatography (GC) was used to determine the stability of LC's extraction. CD model was established by the chronic induction of scopolamine (Scop, 1 mg/kg/day) for 1 week. Behavioral tests including morris water maze (MWM) and y-maze were used to evaluate learning and memory abilities of mice after LC's treatments. Immunofluorescence was used to detected the expressions of cFOS, Brdu and Ki67 after LC's treatments. Pharmacological blockade experiments explored the role of α-Amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in LC's treatments for CD and its relationships with regeneration, activities and differentiation of neurons., Results: The results showed that LC was capable of improving spatial learning and memory and spontaneous alternating abilities in Scop-induced mice, which was similar to donepezil. LC could increase the number of cFOS positive cells, which was used as a marker of neuronal activity to upregulate by neuronal activities in hippocampus, but donepezil did not. Moreover, LC could strengthen neurogenesis and neuro-differentiation by increasing the number of Brdu and Ki67 positive cells in hippocampal dentate gyrus (DG), meanwhile, donepezil could only enhance the number of Ki67 positive cells. Transient inhibition of AMPAR by NBQX blunted the function of LC's treatment for CD and inhibited the enhanced effect of LC on Scop-induced hippocampal neuronal excitability and neurogenesis in mice., Conclusion: To sum up, our study demonstrated that LC had the function of treating CD by enhancing content of acetylcholine (ACh) to activate AMPAR, which further up-regulated neurogenesis and neuronal differentiation to strengthen neuroactivities in hippocampus., Competing Interests: Declaration of competing interest The authors do not have any conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier GmbH.)

Purpose: As the elderly population grows, the prevalence of dementia is also rapidly increasing worldwide. Metformin, an antidiabetic drug, has been shown to have ameliorative effects on impaired cognitive functions in experimental models. However, studies have generally used young animals. Additionally, although it has a major role in Alzheimer's disease (AD) and memory, literature information about the effects of metformin on the cholinergic system is limited. In this study, we investigated the effects of metformin on memory in a model of scopolamine-induced memory impairment in aged rats. We also examined the effects of metformin on the cholinergic system, which is very important in cognitive functions., Methods: Metformin was administered orally to male Wistar rats (20-22 months old) at 100 mg/kg/day for three weeks. Morris water maze (MWM) tests were performed to assess spatial memory. Before the probe test of the MWM test, scopolamine was injected intraperitoneally at a dose of 1 mg/kg. After testing, animals were sacrificed, whole brains were removed, and hippocampus samples were separated for biochemical analysis., Results: Impaired memory associated with scopolamine administration was reversed by metformin. In addition, metformin administration ameliorated scopolamine-induced changes in acetylcholine (ACh) levels, acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and choline acetyltransferase (ChAT) activity., Conclusion: Our results show that metformin may have protective effects in a scopolamine-induced memory impairment model in aged animals by improving cholinergic function. Metformin shows promise in preventing dementia with its dual cholinesterase inhibition and ChAT activation effect., Competing Interests: Conflict of Interest The author does not declare any conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In the present study, we investigated the effect of high-intensity interval training (HIIT) on cognitive behaviors in female rats with a high-fat diet + streptozotocin (STZ)-induced type 2 diabetes., Methods: Twenty-four female rats were divided into four groups randomly (n = 6): control (C), control + exercise (Co + EX), diabetes mellitus (type 2) (T2D), and diabetes mellitus + exercise (T2D + EX). Diabetes was induced by a two-month high-fat diet and a single dose of STZ (35 mg/kg) in the T2D and T2D + EX groups. The Co + EX and T2D + EX groups performed HIIT for eight weeks (five sessions per week, running on a treadmill at 80-100% of V Max , 4-10 intervals). Elevated plus maze (EPM) and open field test (OFT) were used for assessing anxiety-like behaviors, and passive avoidance test (PAT) and Morris water maze (MWM) were applied for evaluating learning and memory. The hippocampal levels of beta-amyloid (Aβ) and Tau were also assessed using Western blot., Results: An increase in fasting blood glucose (FBG), hippocampal level of Tau, and a decrease in the percentage of open arm time (%OAT) as an index of anxiety-like behavior were seen in the female diabetic rats which could be reversed by HIIT. In addition, T2D led to a significant decrease in rearing and grooming in the OFT. No significant difference among groups was seen for the latency time in the PAT and learning and memory in the MWM., Conclusions: HIIT could improve anxiety-like behavior at least in part through changes in hippocampal levels of Tau., (© 2024. The Author(s).)

Objective: Orofacial pain with high prevalence is one of the substantial human health issues. The importance of this matter became more apparent when it was revealed that orofacial pain, directly and indirectly, affects cognition performances. Currently, researchers have focused on investigating pharmaceutics to alleviate pain and ameliorate its subsequent cognitive impairments., Design: In this study, the rats were first treated with the central administration of methyl jasmonate (MeJA), which is an antioxidant and anti-inflammatory bio-compound. After 20 min, orofacial pain was induced in the rats by the injection of capsaicin in their dental pulp. Subsequently, the animals' pain behaviors were analyzed, and the effects of pain and MeJA treatments on rats learning and memory were evaluated/compared using the Morris water maze (MWM) test. In addition, the expression of tumor necrosis factor-α (TNF-α), IL-1β, BDNF, and COX-2 genes in the rats' hippocampus was evaluated using real-time polymerase chain reaction., Results: Experiencing orofacial pain resulted in a significant decline in the rats learning and memory. However, the central administration of 20 μg/rat of MeJA effectively mitigated these impairments. In the MWM, the performance of the MeJA-treated rats showed a two- to threefold improvement compared to the nontreated ones. Moreover, in the hippocampus of pain-induced rats, the expression of pro-inflammatory factors TNF-α, IL-1β, and COX-2 significantly increased, whereas the BDNF expression decreased. In contrast, MeJA downregulated the pro-inflammatory factors and upregulated the BDNF by more than 50%., Conclusions: These findings highlight the notable antinociceptive potential of MeJA and its ability to inhibit pain-induced learning and memory dysfunction through its anti-inflammatory effect., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: Loss of occlusal support due to tooth loss has been indicated as one of the risk factors for Alzheimer's disease. This study aimed to investigate the relationship between tooth loss and cognitive dysfunction and illustrate the role of neuroinflammation in advancing Alzheimer's disease., Materials and Methods: Male 5-month-old senescence-accelerated mouse strain P8 (SAMP8) mice were divided into three groups (n = 7): the C (control), S (sham-operated), and TL (tooth loss) groups. The Morris water maze (MWM) test was performed to assess spatial memory. Additionally, histopathological and molecular assessments of hippocampal tissues were performed., Results: The TL groups exhibited impaired spatial memory in the water maze. Tooth loss induced higher protein expression levels of the neuroinflammation cytokine interleukin-1β (IL-1β) in the hippocampus than in the S and C groups. Tooth loss activated the NLRP3 inflammasome and increased the expression of Caspase-1 in the hippocampus., Conclusions: The findings indicated that tooth loss impairs cognitive function in SAMP8 mice and is closely related to the activation of NLRP3/Caspase-1 in the hippocampus., (© 2023 Wiley Periodicals LLC.)

Diazinon (DZN) an organophosphate (OP), with the most important mechanism of action of DZN being induction of oxidative stress (OS) and inhibition of the enzyme acetylcholinesterase (AChE). Verbascum cheiranthifolium (VER) and Biebersteinia multifida (BM) belong to the Scrophulariaceae and Biebersteiniaceae family respectively. These plants are widely used in Iranian traditional medicine due to their beneficial effects. Thus, this research aimed to appraise the protective effects of the methanolic extract of the VER and BM on changes in the level of expression of α7 and α4 subunits of nicotinic acetylcholine receptors (nAChRs) in hippocampus (HPC) of DZN-treated rats. In this research, 36 male Wistar rats were used and randomly divided into six groups: Control, DZN (40 mg/kg), VER (1 g/kg), DZN+VER (40 mg/kg+1 g/kg), BM (150 mg/kg), and DZN+BM (40 mg/kg+150 mg/kg). At the end of treatment periods, the animals of all groups underwent the Morris water maze (MWM) test. The rats were anesthetized, and blood sampling was performed. Eventually, the brain was removed for histological study and evaluation of OS parameters. The results indicated that DZN increased the extent of expression of nAChRs in the HPC and significantly inhibited cholinesterase (ChEs) activity plus OS parameters. Also, in MWM, the time to find the platform was significantly longer in the DZN group, while the time and the distance in the probe test were lower than in the control groups. VER and BM extract in the treatment groups simultaneously improved the extent of expression of nAChRs, ChEs activity, as well as the parameters of OS and spatial memory significantly. In conclusion, our results support the neuroprotective properties of VER and BM extract versus DZN in rats. Accordingly, the extracts of VER and BM may be useful as an approach for the treatment of learning disorders and memory enhancement., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)