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Hypernatremia is an increase in serum sodium concentration above 145 mmol/L. There are many causes of elevated sodium levels in the blood serum. One is incorrect actions performed by medical staff. The symptoms of excessively high serum sodium levels depend on the severity of hypernatremia, the rate of its increase and the accompanying volume disorders. Severe symptoms include altered consciousness, increased muscle tone and reflexes, convulsions, psychomotor hyperactivity or drowsiness (up to coma), respiratory failure, and even death. We present the case of a 45‐year‐old man who took seven tablets of a blood pressure‐lowering drug, and paramedics subsequently administered a concentrated solution of table salt to induce vomiting. However, vomiting did not occur, leading to hypernatremia. Ultimately, the man survived but developed persistent cognitive dysfunction, including disordered short‐term memory and encoding and retrieval of information from long‐term memory, weakening of attention function and fatigue, and disorders in abstract thinking. The patient's family went to the prosecutor's office to investigate the possibility of medical malpractice. Experts found that the paramedics' actions were incorrect. Although it has been known for many years that table salt solutions should not be used to induce vomiting, unfortunately, both laypeople and medical professionals are still using this technique. Iatrogenic salt poisoning may end not only in serious health complications but also in legal consequences. [ABSTRACT FROM AUTHOR]

Dopamine D3 receptors (D3Rs) modulate neuronal activity in several brain regions including the hippocampus. Although previous studies reported that blocking D3Rs exerts pro‐cognitive effects, their involvement in hippocampal synaptic function and memory in the healthy and aged brain has not been thoroughly investigated. We demonstrated that in adult wild type (WT) mice, D3R pharmacological blockade or genetic deletion as in D3 knock out (KO) mice, converted the weak form of long‐term potentiation (LTP1) into the stronger long‐lasting LTP (LTP2) via the cAMP/PKA pathway, and allowed the formation of long‐term memory. D3R effects were mainly mediated by post‐synaptic mechanisms as their blockade enhanced basal synaptic transmission (BST), AMPAR‐mediated currents, mEPSC amplitude, and the expression of the post‐synaptic proteins PSD‐95, phospho(p)GluA1 and p‐CREB. Consistently, electron microscopy revealed a prevalent expression of D3Rs in post‐synaptic dendrites. Interestingly, with age, D3Rs decreased in axon terminals while maintaining their levels in post‐synaptic dendrites. Indeed, in aged WT mice, blocking D3Rs reversed the impairment of LTP, BST, memory, post‐synaptic protein expression, and PSD length. Notably, aged D3‐KO mice did not exhibit synaptic and memory deficits. In conclusion, we demonstrated the fundamental role of D3Rs in hippocampal synaptic function and memory, and their potential as a therapeutic target to counteract the age‐related hippocampal cognitive decline. [ABSTRACT FROM AUTHOR]

The massive use of herbicides, particularly glyphosate‐based herbicides (GBHs), raises several worries, notably their neurotoxic effects. Several studies have explored the consequences of developmental exposure. Our work aims to determine the impact of maternal exposure to GBH on behavioral disorders and memory deficits, as well as the involvement of oxidative stress in the hippocampus and prefrontal cortex. In addition, our study explores the neuroprotective properties of melatonin in male and female offspring. Pregnant Wistar rats were injected with GBH 75 mg/kg during gestation and lactation. After weaning, the offspring were treated with melatonin (4 mg/kg) from postnatal days 30–58. Our results show that GBH increases anxiety‐like behavior levels in offspring, as well as depression‐like behavior. GBH also impairs working memory in progeny. While markers of oxidative stress show a disturbance in lipid peroxidation and catalase activity, with a more pronounced effect in females, on the other hand, melatonin considerably attenuated the neurotoxic impact observed in the offspring, with higher efficacy in females. The oxidative stress results confirm the antioxidant power of melatonin to counteract the damaging effects of exposure to environmental contaminants such as glyphosate‐based pesticides. It will then be interesting to further our work to fully understand the sex‐dependent effect of melatonin. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative condition in which clinical symptoms are highly correlated with the loss of glutamatergic synapses. While later stages of AD are associated with markedly decreased glutamate levels due to neuronal loss, in the early stages, pathological accumulation of glutamate and hyperactivity contribute to AD pathology and cognitive dysfunction. There is increasing awareness that presynaptic dysfunction, particularly synaptic vesicle (SV) alterations, play a key role in mediating this early‐stage hyperactivity. In the current study, we sought to determine whether the 3xTg mouse model of AD that exhibits both beta‐amyloid (Aβ) and tau‐related pathology would exhibit similar presynaptic changes as previously observed in amyloid or tau models separately. Hippocampal cultures from 3xTg mice were used to determine whether presynaptic vesicular glutamate transporters (VGlut) and glutamate are increased at the synaptic level while controlling for postsynaptic activity. We observed that 3xTg hippocampal cultures exhibited increased VGlut1 associated with an increase in glutamate release, similar to prior observations in cultures from tau mouse models. However, the SV pool size was also increased in 3xTg cultures, an effect not previously observed in tau mouse models but observed in Aβ models, suggesting the changes in pool size may be due to Aβ and not tau. Second, we sought to determine whether treatment with troriluzole, a novel 3rd generation tripeptide prodrug of the glutamate modulator riluzole, could reduce VGlut1 and glutamate release to restore cognitive deficits in 8‐month‐old 3xTg mice. Treatment with troriluzole reduced VGlut1 expression, decreased basal and evoked glutamate release, and restored cognitive deficits in 3xTg mice. Together, these findings suggest presynaptic alterations are early events in AD that represent potential targets for therapeutic intervention, and these results support the promise of glutamate‐modulating drugs such as troriluzole in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer's disease (AD) risk; however, the underlying mechanisms are not fully understood. Here, it is found that the injection of chondroitinase ABC (ChABC), mimicking ECM remodeling, into the medial prefrontal cortex (mPFC) reversed short‐term memory loss and reduced amyloid‐beta (Aβ) deposition in 5xFAD mice. ECM remodeling also reactivated astrocytes, reduced the levels of aggrecan in Aβ plaques, and enhanced astrocyte recruitment to surrounding plaques. Importantly, ECM remodeling enhanced the autophagy‐lysosome pathway in astrocytes, thereby mediating Aβ clearance and alleviating AD pathology. ECM remodeling also promoted Aβ plaque phagocytosis by astrocytes by activating the astrocytic phagocytosis receptor MERTK and promoting astrocytic vesicle circulation. The study identified a cellular mechanism in which ECM remodeling activates the astrocytic autophagy‐lysosomal pathway and alleviates AD pathology. Targeting ECM remodeling may represent a potential therapeutic strategy for AD and serve as a reference for the treatment of this disease. [ABSTRACT FROM AUTHOR]

Early life, or juvenility, stands out as the most pivotal phase in neurodevelopment due to its profound impact over the long‐term cognition. During this period, significant changes are made in the brain's connections both within and between different areas, particularly in tandem with the development of more intricate behaviors. The hippocampus is among the brain regions that undergo significant postnatal remodeling, including dendritic arborization, synaptogenesis, the formation of complex spines and neuron proliferation. Given the crucial role of the hippocampus in spatial memory processing, it has been observed that spatial memory abilities continue to develop as the hippocampus matures, particularly before puberty. The N‐methyl‐d‐aspartate (NMDA) type of glutamate receptor channel is crucial for the induction of activity‐dependent synaptic plasticity and spatial memory formation in both rodents and humans. Although extensive evidence shows the role of NMDA receptors (NMDAr) in spatial memory and synaptic plasticity, the studies addressing the role of NMDAr in spatial memory of juveniles are sparse and mostly limited to adult males. In the present study, we, therefore, aimed to investigate the effects of systemic NMDAr blockade by the MK‐801 on spatial memory (novel object location memory, OLM) and hippocampal plasticity in the form of long‐term potentiation (LTP) of both male and female juvenile rats. Our results show the sex‐dimorphic role of NMDAr in spatial memory and plasticity during juvenility, as systemic NMDAr blockade impairs the OLM and LTP in juvenile males without an effect on juvenile females. Taken together, our results demonstrate that spatial memory and hippocampal plasticity are NMDAr‐dependent in juvenile males and NMDAr‐independent in juvenile females. These sex‐specific differences in the mechanisms of spatial memory and plasticity may imply gender‐specific treatment for spatial memory disorders even in children. [ABSTRACT FROM AUTHOR]

Monosodium glutamate (MSG) is a flavor‐enhancing compound used to elevate the flavor profiles of various foods. This flavor enhancer is the sodium salt of L‐glutamic acid and is widely used in foods, such as flavorings, seasonings, sauces, and instant soups. The potential health effects of MSG consumption, particularly the health issues that excessive consumption could lead to, have been the focus of social concerns. It is stated that excessive consumption of MSG can cause cardiovascular diseases, obesity and diabetes, kidney damage, hypertension, anxiety, and memory impairment. The maximum permissible amount of MSG in foods is set at 10 g/kg according to the Turkish Food Codex. The aim of this study is to develop an appropriate method for analyzing the MSG content within the various food samples like flavorings, seasonings, and spices sold in Turkish local markets. The validation parameters of the developed method were examined and it was found that the developed method corresponds to the recommended values. The limit of detection and the limit of quantitation values were calculated as 4.78 ng/mL and 15.93 ng/mL, respectively. Recovery % was determined to be 100.96% in intra‐day and 132.22% in inter‐day analyses for the precision of the method. The results compared to the values specified in the Turkish Food Codex Food Additives Regulation and samples that purportedly did not contain MSG on their labels were found to contain MSG. [ABSTRACT FROM AUTHOR]

Studies of the impact of brain injury on memory processes often focus on the quantity and episodic richness of those recollections. Here, we argue that the organization of one's recollections offers critical insights into the impact of brain injury on functional memory. It is well‐established in studies of word list memory that free recall of unrelated words exhibits a clear temporal organization. This temporal contiguity effect refers to the fact that the order in which word lists are recalled reflects the original presentation order. Little is known, however, about the organization of recall for semantically rich materials, nor how recall organization is impacted by hippocampal damage and memory impairment. The present research is the first study, to our knowledge, of temporal organization in semantically rich narratives in three groups: (1) Adults with bilateral hippocampal damage and severe declarative memory impairment, (2) adults with bilateral ventromedial prefrontal cortex (vmPFC) damage and no memory impairment, and (3) demographically matched non‐brain‐injured comparison participants. We find that although the narrative recall of adults with bilateral hippocampal damage reflected the temporal order in which those narratives were experienced above chance levels, their temporal contiguity effect was significantly attenuated relative to comparison groups. In contrast, individuals with vmPFC damage did not differ from non‐brain‐injured comparison participants in temporal contiguity. This pattern of group differences yields insights into the cognitive and neural systems that support the use of temporal organization in recall. These data provide evidence that the retrieval of temporal context in narrative recall is hippocampal‐dependent, whereas damage to the vmPFC does not impair the temporal organization of narrative recall. This evidence of limited but demonstrable organization of memory in participants with hippocampal damage and amnesia speaks to the power of narrative structures in supporting meaningfully organized recall despite memory impairment. [ABSTRACT FROM AUTHOR]

Mild–moderate traumatic brain injuries (TBIs) are prevalent, and while many individuals recover, there is evidence that a significant number experience long‐term health impacts, including increased vulnerability to neurodegenerative diseases. These effects are influenced by other risk factors, such as cardiovascular disease. Our study tested the hypothesis that a pre‐injury reduction in cerebral blood flow (CBF), mimicking cardiovascular disease, worsens TBI recovery. We induced bilateral carotid artery stenosis (BCAS) and a mild–moderate closed‐head TBI in male and female mice, either alone or in combination, and analyzed CBF, spatial learning, memory, axonal damage, and gene expression. Findings showed that BCAS and TBI independently caused a ~10% decrease in CBF. Mice subjected to both BCAS and TBI experienced more significant CBF reductions, notably affecting spatial learning and memory, particularly in males. Additionally, male mice showed increased axonal damage with both BCAS and TBI compared to either condition alone. Females exhibited spatial memory deficits due to BCAS, but these were not worsened by subsequent TBI. Gene expression analysis in male mice highlighted that TBI and BCAS individually altered neuronal and glial profiles. However, the combination of BCAS and TBI resulted in markedly different transcriptional patterns. Our results suggest that mild cerebrovascular impairments, serving as a stand‐in for preexisting cardiovascular conditions, can significantly worsen TBI outcomes in males. This highlights the potential for mild comorbidities to modify TBI outcomes and increase the risk of secondary diseases. [ABSTRACT FROM AUTHOR]

Behavioral changes or neuropsychiatric symptoms (NPSs) are common features in dementia and are associated with accelerated cognitive impairment and earlier deaths. However, how NPSs are intertwined with cognitive decline remains elusive. In this study, we identify that the basolateral amygdala (BLA) is a key brain region that is associated with mood disorders and memory decline in the AD course. During the process from pre‐ to post‐onset in AD, the dysfunction of parvalbumin (PV) interneurons and pyramidal neurons in the amygdala leads to hyperactivity of pyramidal neurons in the basal state and insensitivity to external stimuli. We further demonstrate that serotonin (5‐HT) receptors in distinct neurons synergistically regulate the BLA microcircuit of AD rather than 5‐HT levels, in which both restrained inhibitory inputs by excessive 5‐HT1AR signaling in PV interneurons and depolarized pyramidal neurons via upregulated 5‐HT2AR contribute to aberrant neuronal hyperactivity. Downregulation of these two 5‐HT receptors simultaneously enables neurons to resist β‐amyloid peptides (Aβ) neurotoxicity and ameliorates the mood and cognitive defects. Therefore, our study reveals a crucial role of 5‐HT receptors for regulating neuronal homeostasis in AD pathogenesis, and this would provide early intervention and potential targets for AD cognitive decline. [ABSTRACT FROM AUTHOR]

The article revisits the meaning of cognitive impairment in older adults using the Aging, Demographics and Memory Study (ADAMS). Topics discussed include the methods used in the study, the performance of Mini-Mental State Examination (MMSE) as a screening tool for dementia, and the clinical implications of a low MMSE score.

Background: Dementia is assumed to alter mental capacity, which may necessitate legal guardianship. However, only limited research exists on how dementia affects mental capacity, and most studies have focused solely on a medical perspective and concentrate on memory functions. The aim of this qualitative study was to investigate physicians' and legal experts' perceptions on a broad range of cognitive and neuropsychiatric domains potentially affecting mental capacity and the need for guardianship in people with dementia. Methods: Physicians (N = 30) and legal experts (N = 20) participated in semi‐structured individual interviews. The data were analyzed by using content analysis and further semi‐quantified according to the cognitive and neuropsychiatric domains. Results: Physicians considered neuropsychiatric symptoms and executive dysfunction to be the most important deficits in the legal context, while legal experts highlighted episodic memory impairment and dyscalculia. Perceptions regarding the importance of several cognitive and neuropsychiatric symptoms varied between and within the professional groups. Conclusions: Physicians and legal experts diverged in their perceptions of cognitive and neuropsychiatric domains affecting mental capacity and the need for guardianship. The evaluation and influence of medical evidence among legal experts heavily rely on subjective opinions. Given the substantial potential impact on patients' equal access to their rights, developing standardized guidelines is essential. [ABSTRACT FROM AUTHOR]

Background: Tau‐first cognitive proteinopathy (TCP) denotes a clinical phenotype of Alzheimer disease (AD) showing Florzolotau(18F) positron emission tomography (PET) positivity but a negative amyloid status. Aim: We explored the biological property of tau using longitudinal cognitive and neuroimaging data in TCP and compared with late‐onset AD (LOAD). Method: We enrolled 56 patients with LOAD, 34 patients with TCP, and 26 cognitive unimpaired controls. All of the participants had historical data of 2 to 4 three‐dimensional T1 images and 2 to 6 annual cognitive evaluations over a follow‐up period of 7 years. Tau topography was measured using Florzolotau(18F) PET. In the LOAD and TCP groups, we constructed tau or gray matter clusters covarying with the cognitive measurements. We used mediator analysis to explore the regional tau load as predictor, gray matter partitions as mediators, and significant cognitive test scores as outcomes. Longitudinal cognitive decline and cortical thickness degeneration pattern were analyzed using a linear mixed‐effects model. Results: The TCP group had longitudinal declines in nonexecutive domains. The deterministic factor predicting the short‐term memory score in TCP was the hippocampal volume and not directly via the medial and lateral temporal tau load. These features formed the conceptual differences with LOAD. Discussion: The biological properties of tau and the longitudinal cognitive‐imaging trajectory support the conceptual distinction between TCP and LOAD. TCP represents one specific entity featuring salient short‐term memory impairment, declines in nonexecutive domains, a slower gray matter degenerative pattern, and a restricted impact of tau. [ABSTRACT FROM AUTHOR]

Objective: Ethanol (Eth) intake is known to cause numerous detrimental effects on the structure and function of the brain, and it is commonly used as a psychostimulant drug by adolescents. Conversely, omega‐3 (O3) can reduce the risk of cognitive decline and promote the maintenance of neurophysiological functions. In this study, we investigated the protective effects of O3 on behavioral alterations, oxidative stress, and interleukin‐6 (IL‐6) levels induced by chronic Eth intake during adolescence in rats. Materials and methods: Adolescent male rats (21 days old) were divided as follows: (1) Vehicle, (2) Eth (Eth in drinking water [20%]), (3–5) Eth + O3 (50/100/150 mg/kg), and (6) O3 (150 mg/kg). After 5 weeks, Morris water maze (MWM) and passive avoidance (PA) tests were performed, and the hippocampal and cortical levels of oxidative stress markers and inflammatory indices were measured. Results: Adolescent Eth intake impairs learning and memory function in MWM and PA tests (groups × day, p < 0.05 and p < 0.001, respectively). It was shown that Eth induced oxidative stress and neuroinflammation. O3 improved learning and impairment induced by Eth by reducing the adverse effects of Eth on the oxidant/antioxidant balance in the hippocampi (for malondialdehyde [MDA]/thiol: p < 0.01, p < 0.001, respectively) and for superoxide dismutase (SOD)/catalase (CAT): p < 0.01 and p < 0.05, respectively). Furthermore, we found that O3 prevented the Eth‐induced increase of hippocampal IL‐6 (p < 0.001). Conclusion: O3 supplementation acts as an effective approach to prevent learning and memory impairments induced by chronic Eth consumption during adolescence. In this respect, the antioxidant and anti‐inflammatory properties of O3 seem to be the main underlying mechanisms of neuroprotection. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions The aim of this study was to examine the discriminative validity of the Brief Assessment of Impaired Cognition (BASIC) case‐finding instrument in a general practice (GP) setting and compare it with other widely used brief cognitive instruments.Patients aged ≥70 years were prospectively recruited from 14 Danish GP clinics. Participants were classified as having either normal cognition (n = 154) or cognitive impairment (n = 101) based on neuropsychological test performance, reported instrumental activities of daily living, and concern regarding memory decline. Comparisons involved the Mini‐Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Rowland Universal Dementia Assessment Scale (RUDAS), the Mini‐Cog, the 6‐item Clock Drawing Test (CDT‐6) and the BASIC Questionnaire (BASIC‐Q).BASIC demonstrated good overall classification accuracy with an area under the receiver operating characteristic curve (AUC) of 0.88 (95% confidence interval [CI] 0.84–0.92), a sensitivity of 0.72 (95% CI 0.62–0.80) and a specificity of 0.86 (95% CI 0.79–0.91). Pairwise comparisons of the AUCs of BASIC, MMSE, MoCA and RUDAS produced non‐significant results, but BASIC had significantly higher classification accuracy than Mini‐Cog, BASIC‐Q and CDT‐6. Depending on the pretest probability of cognitive impairment, the positive predictive validity of BASIC varied from 0.83 to 0.36, and the negative predictive validity from 0.97 to 0.76.BASIC demonstrated good discriminative validity in a GP setting. The classification accuracy of BASIC is equivalent to more complex, time‐consuming instruments, such as the MMSE, MoCA and RUDAS, and higher than very brief instruments, such as the CDT‐6, Mini‐Cog and BASIC‐Q. [ABSTRACT FROM AUTHOR]

Objective: To identify the most relevant clinical characteristics of the nursing diagnosis frail elderly syndrome (FES) in hospitalized patients aged 65 or older and analyze their impact on 9‐month mortality and hospital readmission. Methods: A prospective and prognostic accuracy study was conducted in patients aged 65 or older, who were admitted to hospital more than 24 h. A consecutive convenience sampling process was used. Assessment included defining characteristics (DCs) of FES, clinical fraility scale (CFS), frail scale (FS), and 9‐month mortality and hospital readmission. Statistical tests were used to verify associations between variables. Binary logistic regression analysis and area under the curve were used, to identify significant predictors for the outcomes and evaluate the prognostic accuracy of the DCs. Findings: This study involved 150 patients. CFS scored 65 patients (43.3%, confidence interval 95% 35.2% a 51.6) as frail and proved a prognostic value of mortality at 9 month from pre‐frail state (p = 0.020). The mean number of DCs for FES nursing diagnosis was 6.35 (SD = 3.14). Validated tools for measuring frailty were associated with all DCs, excepting nutritional imbalance: below body needs. The hospital readmission during the following 9 months was only statistically related to memory impairment (p = 0.07). Conclusion: Clinical frailty scale showed good results as a predictor of mortality. The study suggests exploring including it, in clinical manifestations of elderly frail syndrome. This study found that only memory impairment defining characteristic was predictive of hospital readmission. Further research should identify other relevant and prognostic clinical manifestations. Implication for nursing practice: These findings highlight the importance of being vigilant on cognitive decline during hospital admissions. The most prevalent and determinant DCs identified in this study indicate that clinical should focus on preserving functional and mental abilities as well as mobility. [ABSTRACT FROM AUTHOR]

We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para‐aminosalicylate (PAS‐Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y‐maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS‐Na displayed some antagonistic effects against the Mn‐ and Fe‐induced synaptic structural damage, growth, learning and memory impairment. [ABSTRACT FROM AUTHOR]

Gut dysbiosis is linked to metabolic and neurodegenerative diseases and comprises a plausible link between high‐fat diet (HFD) and brain dysfunction. Here we show that gut microbiota modulation by either antibiotic treatment for 5 weeks or a brief 3‐day fecal microbiota transplantation (FMT) regimen from low‐fat (control) diet‐fed mice decreased weight gain, adipose tissue hypertrophy, and glucose intolerance induced by HFD in C57BL/6 male mice. Notably, gut microbiota modulation by FMT completely reversed impaired recognition memory induced by HFD, whereas modulation by antibiotics had less pronounced effect. Improvement in recognition memory by FMT was accompanied by decreased HFD‐induced astrogliosis in the hippocampal cornu ammonis region. Gut microbiome composition analysis indicated that HFD diminished microbiota diversity compared to control diet, whereas FMT partially restored the phyla diversity. Our findings reinforce the role of the gut microbiota on HFD‐induced cognitive impairment and suggest that modulating the gut microbiota may be an effective strategy to prevent metabolic and cognitive dysfunction associated with unfavorable dietary patterns. [ABSTRACT FROM AUTHOR]

Inflammation and oxidative stress upset memory. We explored influence of sodium nitroprusside (SNP) on memory deficits resulted from lipopolysaccharide (LPS).Groups include control, LPS, LPS + SNP 1 mg/kg, LPS + SNP 2 mg/kg, and LPS + SNP 3 mg/kg. Morris water maze and passive avoidance tests and biochemical measurements were carried out.In Morris water maze, LPS prolonged time and distance for finding the platform. In probe trial, it diminished time spent and traveled distance in the target zone. Injection of 2 and 3 mg/kg of SNP overturned the effect of LPS. In passive avoidance task, LPS postponed entrance into darkroom and reduced time spent in light room and incremented time spent in darkroom in 3, 24, and 72 h after electrical shock. All three doses of SNP restored the effects of LPS. Biochemical experiments confirmed that LPS elevated interleukin‐6 and malondialdehyde concentration and declined total thiol content and superoxide dismutase and catalase activity in the hippocampus and cortex tissues. SNP particularly at a 3 mg/kg dose ameliorated LPS effects on these parameters.SNP attenuated memory disabilities resulting from LPS through modifying inflammation and boosting antioxidant defense. [ABSTRACT FROM AUTHOR]

Objective: Brain infection with Theiler's murine encephalomyelitis virus (TMEV) in C57BL/6J mice can induce acquired epileptogenesis. Diet alters acute seizure incidence in TMEV‐infected mice; yet it is unclear whether intestinal dysbiosis may also impact acute or chronic behavioral comorbidities. This study thus assessed the impact of diet formulation and sterilization on acute seizure presentation, gut microbiome composition, and epilepsy‐related chronic behavioral comorbidities. Methods: Baseline fecal samples were collected from male C57BL/6J mice (4‐ to 5‐weeks‐old; Jackson Labs) upon facility arrival. Mice were randomized to either autoclaved (AC) or irradiated diet (IR) (Prolab RMH 3000) or IR (Picolab 5053). Three days later, mice underwent intracerebral TMEV or phosphate‐buffered saline (PBS) injection. Fecal samples were collected from a subset of mice at infection (Day 0) and Day 7 post‐infection. Epilepsy‐related working memory deficits and seizure threshold were assessed 6 weeks post‐infection. Gut microbiome diversity was determined by 16S rRNA amplicon sequencing of fecal samples. Results: TMEV‐infected mice displayed acute handling‐induced seizures, regardless of diet: 28 of 57 IR Picolab 5053 (49.1%), 30 of 41 IR Prolab RMH 3000 (73.2%), and 47 of 77 AC Prolab RMH 3000 (61%) mice displayed seizures. The number of observed seizures differed significantly by diet: IR Picolab 5053 diet‐fed mice had 2.2 ± 2.8 seizures (mean ± standard deviation), IR Prolab RMH 3000 diet‐fed mice had 3.5 ± 2.9 seizures, and AC Prolab RMH 3000 diet‐fed mice had 4.4 ± 3.8 seizures during the 7‐day monitoring period. Gut microbiome composition differed significantly in TMEV‐infected mice fed the AC Prolab RMH 3000 diet, with measured differences in gram‐positive bacteria. These mice also displayed worsened long‐term working memory deficits. Significance: Diet‐induced differences in intestinal dysbiosis in the TMEV model are associated with marked changes in acute seizure presentation, symptomatic recovery, and onset of chronic behavioral comorbidities of epilepsy. Our study reveals a novel disease‐modifying impact of dietary manipulation on intestinal bacterial species after TMEV‐induced acute seizures. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a complex and common neurodegenerative disorder. The present study aimed to investigate the potential effects of selegiline (SEL) on various aspects of memory performance, anxiety, and oxidative stress in an AD rat model induced by intracerebroventricular injection of amyloid beta1‐42 (Aβ1‐42). Methods: Oral administration of SEL at a dose of 0.5 mg/kg/day was performed for 30 consecutive days. Following the 30 days, several tests, including the open‐field, elevated plus‐maze, novel object recognition, Morris water maze, and passive avoidance learning were conducted to assess locomotor activity, anxiety‐like behavior, recognition memory, spatial memory, and passive avoidance memory, respectively. Results: The results indicate that the induction of AD in rats led to recognition memory, spatial memory, and passive avoidance memory impairments, as well as increased anxiety. Additionally, the AD rats exhibited a decrease in total antioxidant capacity and an increase in total oxidant status levels, suggesting an imbalance in oxidative‐antioxidant status. However, the administration of SEL improved memory performance, reduced anxiety, and modulated oxidative‐antioxidant status in AD rats. Conclusions: These findings provide evidence that SEL may alleviate anxiety‐like behavior and cognitive deficits induced by Aβ through modulation of oxidative‐antioxidant status. [ABSTRACT FROM AUTHOR]

Aims: Synaptic dysfunction is a hallmark pathology of Alzheimer's disease (AD) and is strongly associated with cognitive impairment. Abnormal phagocytosis by the microglia is one of the main causes of synapse loss in AD. Previous studies have shown that the absence of melanoma 2 (AIM2) inflammasome activity is increased in the hippocampus of APP/PS1 mice, but the role of AIM2 in AD remains unclear. Methods: Injection of Aβ1‐42 into the bilateral hippocampal CA1 was used to mimic an AD mouse model (AD mice). C57BL/6 mice injected with AIM2 overexpression lentivirus and conditional knockout of microglial AIM2 mice were used to confirm the function of AIM2 in AD. Cognitive functions were assessed with novel object recognition and Morris water maze tests. The protein and mRNA expression levels were evaluated by western blotting, immunofluorescence staining, and qRT‐PCR. Synaptic structure and function were detected by Golgi staining and electrophysiology. Results: The expression level of AIM2 was increased in AD mice, and overexpression of AIM2 induced synaptic and cognitive impairments in C57BL/6 mice, similar to AD mice. Elevated expression levels of AIM2 occurred in microglia in AD mice. Conditional knockout of microglial AIM2 rescued cognitive and synaptic dysfunction in AD mice. Excessive microglial phagocytosis activity of synapses was decreased after knockout of microglial AIM2, which was associated with inhibiting complement activation. Conclusion: Our results demonstrated that microglial AIM2 plays a critical role in regulating synaptic plasticity and memory deficits associated with AD, providing a new direction for developing novel preventative and therapeutic interventions for this disease. [ABSTRACT FROM AUTHOR]

Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor‐predisposition disorder. As many as 70% of children with NF1 report difficulties with spatial/working memory, attention, executive function, and fine motor movements. In contrast to the utilization of various Nf1 mouse models, here we employ an NF1+/ex42del miniswine model to evaluate the mechanisms and characteristics of these presentations, taking advantage of a large animal species more like human anatomy and physiology. The prefrontal lobe, anterior cingulate, and hippocampus from NF1+/ex42del and wild‐type miniswine were examined longitudinally, revealing abnormalities in mature oligodendrocytes and astrocytes, and microglial activation over time. Imbalances in GABA: Glutamate ratios and GAD67 expression were observed in the hippocampus and motor cortex, supporting the role of disruption in inhibitory neurotransmission in NF1 cognitive impairment and motor dysfunction. Moreover, NF1+/ex42del miniswine demonstrated slower and shorter steps, indicative of a balance‐preserving response commonly observed in NF1 patients, and progressive memory and learning impairments. Collectively, our findings affirm the effectiveness of NF1+/ex42del miniswine as a valuable resource for assessing cognitive and motor impairments associated with NF1, investigating the involvement of specific neural circuits and glia in these processes, and evaluating potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Aim: Being front‐line healthcare professionals is associated with possible severe information anxiety during the COVID‐19 pandemic. Investigating signs of information anxiety is the first and key step of its targeted medical intervention. This study aims to explore the signs of front‐line healthcare professionals' information anxiety during the COVID‐19 pandemic. Design: This study is qualitative research. Grounded theory was used to classify information anxiety signs of front‐line healthcare professionals. Methods: Twenty‐four front‐line healthcare professionals from a general hospital with over 5000 beds in Wuhan were recruited to participate in semi‐structured interviews. According to the frequency and frequency variation of signs appearing in interviews, the trends of signs during the virus encounter, lockdown, flattening and second wave were compared. Based on the interviews, those signs that were conceptually related to each other were extracted to construct a conceptual model. Results: Psychological signs (emotion, worry, doubt, caution, hope), physical signs (insomnia, inattention, memory loss, appetite decreased) and behavioural signs (panic buying of goods, be at a loss, pay attention to relevant information, change habits) could be generalized from 13 subcategories of information anxiety signs. Psychological signs were the most in every period of the pandemic. Furthermore, psychological signs decreased significantly during lockdown, while behavioural and physical signs increased. Finally, severe psychological and behavioural signs were associated with physical signs. [ABSTRACT FROM AUTHOR]

Objectives: Patients with traumatic brain injury (TBI) often suffer memory and cognitive impairments, and oxiracetam‐like drugs are considered to have a positive impact on these symptoms potentially. However, the efficacy and safety of L‐oxiracetam and oxiracetam in TBI patients have not been sufficiently investigated. Methods: The study adopts a multicenter, randomized, double‐blind, parallel‐group, phase 3 clinical trial design in 74 centers across 51 hospitals in China. A total of 590 TBI patients meeting criteria will be randomly allocated into three groups in a 2:2:1 ratio: L‐oxiracetam group, oxiracetam group, and placebo group. The treatment period is 14 days, with a follow‐up period of 90 days. The primary outcome measure is the change in the Loewenstein Occupational Therapy Cognitive Assessment score at 90 days after treatment. Secondary outcomes include changes in other cognitive assessments, neurological function, activities of daily living, and safety assessments. Discussion: There is no robust evidence to suggest that L‐oxiracetam and oxiracetam can enhance memory and cognitive function in patients with mild to moderate TBI. This study has the potential to answer this crucial clinical question. Trial registration: chinadrugtrials.org.cn, identifier CTR20192539; ClinicalTrials.gov, identifier NCT04205565. [ABSTRACT FROM AUTHOR]

Information storage in the brain involves different memory types and stages that are processed by several brain regions. Cholinergic pathways through acetylcholine receptors actively participate on memory modulation, and their disfunction is associated with cognitive decline in several neurological disorders. During the last decade, the role of α7 subtype of nicotinic acetylcholine receptors in different memory stages has been studied. However, the information about their role in memory processing is still scarce. In this review, we attempt to identify brain areas where α7 nicotinic receptors have an essential role in different memory types and stages. In addition, we discuss recent work implicating—or not—α7 nicotinic receptors as promising pharmacological targets for memory impairment associated with neurological disorders. [ABSTRACT FROM AUTHOR]

Introduction: Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti‐inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD‐induced cognitive impairment and its mechanisms are unknown. Methods: In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61–88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme‐linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription‐polymerase chain reaction and western blotting. Results: The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)‐1creIL‐6, and tumor necrosis factor‐α and decreased the expression levels of brain‐derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein‐95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels. Conclusions: These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction. [ABSTRACT FROM AUTHOR]

Background: The inflammation and synaptic dysfunction induced by mitochondrial dysfunction play essential roles in the learning and memory impairment associated with sleep dysfunction. Elamipretide (SS‐31), a novel mitochondrion‐targeted antioxidant, was proven to improve mitochondrial dysfunction, the inflammatory response, synaptic dysfunction, and cognitive impairment in models of cerebral ischemia, sepsis, and type 2 diabetes. However, the potential for SS‐31 to improve the cognitive impairment induced by chronic sleep deprivation (CSD) and its underlying mechanisms is unknown. Methods: Adult c57BL/6J mice were subjected to CSD for 21 days using an activity wheel accompanied by daily intraperitoneal injection of SS‐31 (5 mg/kg). The novel object recognition and Morris water maze test were used to evaluate hippocampus‐dependent cognitive function. Western blotting and reverse transcription‐quantitative polymerase chain reaction assays were used to determine the effects of CSD and SS‐31 on markers of mitochondria, inflammation response, and synaptic function. Enzyme‐linked immunosorbent assays were used to examine the levels of proinflammatory cytokines. Results: SS‐31 could improve the cognitive impairment induced by CSD. In particular, SS‐31 treatment restored the CSD‐induced decrease in sirtuin 1 (SIRT1) and peroxisome proliferator‐activated receptor γ coactivator alpha levels and the increase in levels nuclear factor kappa‐B and inflammatory cytokines, including interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐alpha. Furthermore, SS‐31 significantly increased the levels of brain‐derived neurotrophic factor, postsynaptic density protein‐95, and synaptophysin in CSD mice. Conclusion: Taken together, these results suggest that SS‐31 could improve CSD‐induced mitochondrial biogenesis dysfunction, inflammatory response, synaptic dysfunction, and cognitive impairment by increasing SIRT1 expression levels. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Sevoflurane is a superior agent for maintaining anesthesia during surgical procedures. However, the neurotoxic mechanisms of clinical concentration remain poorly understood. Sevoflurane can interfere with the normal function of neurons and synapses and impair cognitive function by acting on α5‐GABAAR. Methods: Using MWM test, we evaluated cognitive abilities in mice following 1 h of anesthesia with 2.7%–3% sevoflurane. Based on hippocampal transcriptome analysis, we analyzed the differential genes and IL‐6 24 h post‐anesthesia. Western blot and RT‐PCR were performed to measure the levels of α5‐GABAAR, Radixin, P‐ERM, P‐Radixin, Gephyrin, IL‐6, and ROCK. The spatial distribution and expression of α5‐GABAAR on neuronal somata were analyzed using histological and three‐dimensional imaging techniques. Results: MWM test indicated that partial long‐term learning and memory impairment. Combining molecular biology and histological analysis, our studies have demonstrated that sevoflurane induces immunosuppression, characterized by reduced IL‐6 expression levels, and that enhanced Radixin dephosphorylation undermines the microstructural stability of α5‐GABAAR, leading to its dissociation from synaptic exterior and resulting in a disordered distribution in α5‐GABAAR expression within neuronal cell bodies. On the synaptic cleft, the expression level of α5‐GABAAR remained unchanged, the spatial distribution became more compact, with an increased fluorescence intensity per voxel. On the extra‐synaptic space, the expression level of α5‐GABAAR decreased within unchanged spatial distribution, accompanied by an increased fluorescence intensity per voxel. Conclusion: Dysregulated α5‐GABAAR expression and distribution contributes to sevoflurane‐induced partial long‐term learning and memory impairment, which lays the foundation for elucidating the underlying mechanisms in future studies. [ABSTRACT FROM AUTHOR]

Aluminum chloride (AlCl3) is a potent neurotoxic substance known to cause memory impairment and oxidative stress‐dependent neurodegeneration. Naringenin (NAR) is a dietary flavonoid with potent antioxidant and anti‐inflammatory properties which was implemented against AlCl3‐induced neurotoxicity to ascertain its neuroprotective efficacy. Experimental neurotoxicity in mice was induced by exposure of AlCl3 (10 mg/kg, p.o.) followed by treatment with NAR (10 mg/kg, p.o.) for a total of 63 days. Assessed the morphometric, learning memory dysfunction (novel object recognition, T‐ and Y‐maze tests), neuronal oxidative stress, and histopathological alteration in different regions of the brain, mainly cortex, hippocampus, thalamus, and cerebellum. AlCl3 significantly suppressed the spatial learning and memory power which were notably improved by administration of NAR. The levels of oxidative stress parameters nitric oxide, advanced oxidation of protein products, protein carbonylation, lipid peroxidation, superoxide dismutase, catalase, glutathione reductase, reduced glutathione, and the activity of acetylcholine esterase were altered 1.5–3 folds by AlCl3 significantly. Treatment of NAR remarkably restored the level of oxidative stress parameters and maintained the antioxidant defense system. AlCl3 suppressed the expression of neuronal proliferation marker NeuN that was restored by NAR treatment which may be a plausible mechanism. NAR showed therapeutic efficacy as a natural supplement against aluminum‐intoxicated memory impairments and histopathological alteration through a mechanism involving an antioxidant defense system and neuronal proliferation. [ABSTRACT FROM AUTHOR]

Background and Objective: Reduced functional capacity, dyspnea, fatigue, and changes in body composition are common in patients with post‐COVID‐19 syndrome (PCS), and cardiopulmonary rehabilitation may improve these parameters. Thus, the present study verified the effects of cardiopulmonary rehabilitation (respiratory, aerobic, and resistance muscle training) on submaximal exercise tolerance, dyspnea, fatigue, and body composition. Methods: This controlled and randomized clinical trial applied a six‐week outpatient intervention protocol in individuals over 18 years old (n = 33) with a diagnosis of COVID‐19 confirmed by polymerase chain reaction. These individuals were allocated to cardiopulmonary rehabilitation (n = 17) or control groups (i.e., educational lectures; n = 16). The cardiopulmonary rehabilitation group performed respiratory, aerobic, and resistance muscle training. Submaximal exercise tolerance, dyspnea, fatigue, and body composition were assessed before and after the protocol. Results: After 6 weeks, the cardiopulmonary rehabilitation group increased the tolerance to submaximal exercise, with a difference of 100.46 m (95% confidence interval [CI]: 7.40–193 m) in the distance walked on the six‐minute walk test, reduced dyspnea (−1.45, 95% CI: −1.98–−0.92) in the modified Medical Research Council, and increased 0.63 kg (95% CI: 0.09–1.18 kg) of muscle mass in the upper limbs compared with the control group. Conclusion: The six‐week cardiopulmonary rehabilitation protocol improved functional capacity, reduced dyspnea, and increased muscle mass in the upper limbs in individuals with PCS. Thus, these results supported the protocol use in this population and encourage further studies to assess its effectiveness in a large sample. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is a worldwide health concern, especially in the elderly population. Much remains unknown about the relationship between vitamin D deficiency (VDD), stress‐induced cognitive dysfunctions and depressive‐like behaviour. In this study, 4‐month‐old male C57Bl/6J mice were fed with control or vitamin D free diet for 6 months, followed by unpredictable chronic stress (UCMS) for 8 weeks. VDD induced cognitive impairment and reduced grooming behaviour, but did not induce depressive‐like behaviour. While UCMS in vitamin D sufficient mice induced expected depressive‐like phenotype and impairments in the contextual fear memory, chronic stress did not manifest as an additional risk factor for memory impairments and depressive‐like behaviour in VDD mice. In fact, UCMS restored self‐care behaviour in VDD mice. At the histopathological level, VDD mice exhibited cell loss in the granule cell layer, reduced survival of newly generated cells, accompanied with an increased number of apoptotic cells and alterations in glial morphology in the hippocampus; however, these effects were not exacerbated by UCMS. Interestingly, UCMS reversed VDD induced loss of microglial cells. Moreover, tyrosine hydroxylase levels decreased in the striatum of VDD mice, but not in stressed VDD mice. These findings indicate that long‐term VDD in adulthood impairs cognition but does not augment behavioural response to UCMS in middle‐aged mice. While VDD caused cell loss and altered glial response in the DG of the hippocampus, these effects were not exacerbated by UCMS and could contribute to mechanisms regulating altered stress response. [ABSTRACT FROM AUTHOR]

Age‐related dysfunctions in specific neurotransmitter systems likely play an important role in cognitive decline even in its most subtle forms. Therefore, preservation or improvement of cognition via augmentation of neurotransmission is a potential therapeutic strategy to prevent further cognitive deficits. Here we identified a particular neuronal vulnerability in the aged Fischer 344 rat brain, an animal model of neurocognitive aging. Specifically, we demonstrated a marked impairment in glutamate‐stimulated release of norepinephrine (NE) in the hippocampus and cerebral cortex of aged rats, and established that this release was mediated by N‐methyl‐D‐aspartate (NMDA) receptors. Further, we also demonstrated that this decrease in NE release is fully rescued by the psychostimulant drug amphetamine (AMPH). Moreover, we showed that AMPH increases dendritic spine maturation, and importantly shows preclinical efficacy in restoring memory deficits in the aged rat through its actions to potentiate NE neurotransmission at β‐adrenergic receptors. Taken together, our results suggest that deficits in glutamate‐stimulated release of NE may contribute to and possibly be a determinant of neuronal vulnerability underlying cognitive decline during aging, and that these deficits can be corrected with currently available drugs. Overall these studies suggest that repurposing of psychostimulants for age‐associated cognitive deficits is a potential avenue to delay or prevent cognitive decline and/or frank dementia later in life. [ABSTRACT FROM AUTHOR]

Introduction: The potential consequences of repeated concussions in sport are well documented. However, it remains unclear whether the cumulative impact of sports‐related concussions differs between different contact sports. Therefore, the aim of the current study was to investigate the cumulative effects of sports‐related concussions on clinical and neurocognitive health in different contact sports. Materials and Methods: In a prospective multicenter study, we examined 507 (74 females) active professional athletes between 18 and 40 years of age from five different contact sports (soccer, handball, American football, basketball, and ice hockey). Data collection involved concussion history, clinical symptom evaluation, neurocognitive assessment, and the collection of other sports‐related information. Composite scores were built for clinical symptoms (such as neck pain and balance disturbances) and for neurocognitive symptoms (such as memory and attention impairments). Results: Athletes having suffered 3+ concussions in the past showed disproportionally higher clinical symptom severity than athletes with less than three concussions across all sports. The level of clinical symptom burden in athletes with 3+ concussions indicated mild impairment. The number of past concussions did not affect neurocognitive performance. Discussion: Repeated sports‐related concussions appear to have a cumulative impact on clinical—but not cognitive—symptom severity. Although clinical symptom burden in athletes with 3+ concussions in the past was not alarmingly high yet in our sample, increased caution should be advised at this point. Despite few exceptions, results are similar for different contact sports, suggesting a similar multidisciplinary concussion management across all types of sport. [ABSTRACT FROM AUTHOR]

Recently, there has been renewed interest in the effect of lying on memory. A growing body of studies has documented that lying can impair memories and cause memory disruptions, such as forgetting and false memories, to a greater degree than telling the truth. This study aimed to investigate whether motivation plays a role in the effect of lying on memory. The present study utilized a daily life paradigm and manipulated three conditions: truth telling, internally motivated lying, and externally motivated lying. We asked participants to engage in a shopping task and to tell lies (externally motivated lying group) or to choose between telling the truth (truth‐telling group) and telling lies (internally motivated lying group) in the interview. Forty‐eight hours later, the participants were instructed to truthfully carry out multiple memory assessments. The principal findings of this research are that lying can result in memory impairments, and internally motivated lying can lead to greater impairment in source memory than externally motivated lying. Moreover, no significant differences between the two lying groups were found in the memory tests. The empirical findings of this study provide new insights into the effect of lying on memory. [ABSTRACT FROM AUTHOR]

Objective: Children with self‐limited epilepsy characterized by centrotemporal spikes (SeLECTS) exhibit cognitive deficits in memory during the active phase, but there is currently a lack of studies and techniques to assess their memory development after well‐controlled seizures. In this study, we employed eye‐tracking techniques to investigate visual memory and its association with clinical factors and global intellectual ability, aiming to identify potential risk factors by examining encoding and recognition processes. Methods: A total of 26 recruited patients diagnosed with SeLECTS who had been seizure‐free for at least 2 years, along with 24 control subjects, underwent Wechsler cognitive assessment and an eye‐movement‐based memory task while video‐electroencephalographic (EEG) data were recorded. Fixation and pupil data related to eye movements were utilized to detect distinct memory processes and subsequently to compare the cognitive performance of patients exhibiting different regression patterns on EEG. Results: The findings revealed persistent impairments in visual memory among children with SeLECTS after being well controlled, primarily observed in the recognition stage rather than the encoding phase. Furthermore, the age at onset, frequency of seizures, and interictal epileptiform discharges exhibited significant correlations with eye movement data. Significance: Children with SeLECTS exhibit persistent recognition memory impairment after being well controlled for the disease. Controlling the frequency of seizures and reducing prolonged epileptiform activity may improve memory cognitive development. The application of the eye‐tracking technique may provide novel insights into exploring memory cognition as well as underlying mechanisms associated with pediatric epilepsy. [ABSTRACT FROM AUTHOR]

Background: Many clinical evidences have reported the higher risk of seizure in young children and infants after exposure to hyperthermia, which more likely can cause brain damage and affect cognitive function, so, many researches were focused on prevention or treatment of febrile seizure (FS) with minimal adverse effects. Considering the potential effects of oxidative stress as a prominent trigger in FS, and demonstrating the anti‐oxidant effects of metformin, the present study aimed to investigate the protective effect of metformin administration in prenatal and lactation periods in rat pups exposed to hyperthermia by which induced seizure. Method and materials: Pregnant rats were divided into six groups: (1) vehicle: pregnant rats received normal saline during pregnancy and lactation; (2) FS: pregnant rats received normal saline during pregnancy and lactation; (3–5) FS‐Met50/100/150 mg/kg: pregnant rats received different doses of metformin including 50, 100 and 150 mg/kg during pregnancy and lactation; (6) Met150 mg/kg: pregnant rats received Met150 mg/kg during pregnancy and lactation. The male pups born to mothers received in all FS groups exposed to hyperthermia. All experimental groups were allowed to grow up, and after the lactation period, they were subjected for behavioural tests and biochemical analysis. Results: According to the present findings, the prenatal and lactation exposure to the highest dose of metformin demonstrated significant difference with FS group in both behavioural and biochemical test analyses. Although the remaining doses of metformin were also effective, the much better results were reported with the highest dose of metformin (150 mg/kg). Interestingly, the highest dose of metformin administered alone demonstrated better result than vehicle in probe trial test. Conclusion: Considering the present research and related study in relation to metformin in ameliorating the epilepsy symptoms, there are numerous evidences on positive effect of metformin on seizure. Although the exact mechanism is unclear, the anti‐oxidant effect of metformin is strongly supported. [ABSTRACT FROM AUTHOR]

Aims: Ventral pathway circuits are constituted by the interconnected brain areas that are distributed throughout the brain. These brain circuits are primarily involved in processing of object related information in brain. However, their role in object recognition memory (ORM) enhancement remains unknown. Here, we have studied on the implication of these circuits in ORM enhancement and in reversal of ORM deficit in aging. Methods: The brain areas interconnected to ventral pathway circuits in rat brain were activated by an expression of a protein called regulator of G‐protein signaling 14 of 414 amino acids (RGS14414). RGS14414 is an ORM enhancer and therefore used here as a gain‐in‐function tool. ORM test and immunohistochemistry, lesions, neuronal arborization, and knockdown studies were performed to uncover the novel function of ventral pathway circuits. Results: An activation of each of the brain areas interconnected to ventral pathway circuits individually induced enhancement in ORM; however, same treatment in brain areas not interconnected to ventral pathway circuits produced no effect. Further study in perirhinal cortex (PRh), area V2 of visual cortex and frontal cortex (FrC), which are brain areas that have been shown to be involved in ORM and are interconnected to ventral pathway circuits, revealed that ORM enhancement seen after the activation of any one of the three brain areas was unaffected by the lesions in other two brain areas either individually in each area or even concurrently in both areas. This ORM enhancement in all three brain areas was associated to increase in structural plasticity of pyramidal neurons where more than 2‐fold higher dendritic spines were observed. Additionally, we found that an activation of either PRh, area V2, or FrC not only was adequate but also was sufficient for the reversal of ORM deficit in aging rats, and the blockade of RGS14414 activity led to loss in increase in dendritic spine density and failure in reversal of ORM deficit. Conclusions: These results suggest that brain areas interconnected to ventral pathway circuits facilitate ORM enhancement by an increase in synaptic connectivity between the local brain area circuits and the passing by ventral pathway circuits and an upregulation in activity of ventral pathway circuits. In addition, the finding of the reversal of ORM deficit through activation of an interconnected brain area might serve as a platform for developing not only therapy against memory deficits but also strategies for other brain diseases in which neuronal circuits are compromised. [ABSTRACT FROM AUTHOR]

This article discusses a study that examined the effects of co-housing control mice with mice carrying Alzheimer's disease (AD) genes. The researchers found that the control mice that were co-housed with AD mice experienced changes in their gut microbiota and impairment of learning and memory. The study suggests that living with subjects with dementia may lead to gut microbiota changes and cognitive impairment in control subjects. These findings provide insights into the potential role of gut microbiota in AD-like brain changes and highlight the importance of further research in this area. [Extracted from the article]

To address the memory functioning after medial temporal lobe (MTL) surgery for refractory epilepsy and relationships with the side of the hippocampal removal, 22 patients with pharmaco‐resistant epilepsy who had undergone MTL resection (10 right/12 left) at the Salpêtrière Hospital were compared with 21 matched healthy controls. We designed a specific neuropsychological binding memory test that specifically addressed hippocampal cortex functioning, and left–right material‐specific lateralization. Our results showed that both left and right mesial temporal lobe removal cause a severe memory impairment, for both verbal and visual material. The removal of left medial temporal lobe causes worse memory impairment than the right removal regardless of the stimuli type (verbal or visual) questioning the theory of the hippocampal material‐specific lateralization. The present study provided new evidence for the role of both hippocampus and surrounding cortices in memory‐binding whatever the material type and also suggested that a left MTL removal is more deleterious for both verbal and visual episodic memory in comparison with right MTL removal. [ABSTRACT FROM AUTHOR]

Aim: Impairments in emotional memory are frequently observed in several mental disorders, highlighting their significance as potential therapeutic targets. Recent research on the cued fear conditioning model has elucidated the neural circuits involved in fear memory processing. However, contradictory findings have been reported concerning the role of dopamine and the impact of dopamine D2 receptor (D2R) antagonists. There is notably limited knowledge regarding the clinical utility of chronic D2R antagonist treatments. This study aimed to uncover how such treatments affect fear memory processing. Methods: We utilized a cued fear conditioning rat model and conducted chronic haloperidol treatment for 14 days. Subsequently, to investigate the effect of chronic haloperidol treatment on fear‐conditioned memory expression and extinction, we observed freezing behavior under exposure to a conditioned stimulus for 14 days. Results: Chronic haloperidol treatment suppressed freezing time on the fear memory expression. In contrast, a single haloperidol administration enhanced the freezing time on fear memory expression and delayed extinction. Conclusion: The results of this study suggest that chronic administration of antipsychotic drugs affects fear memory processing differently from single‐dose administration. This indicates that the effects of chronic D2R antagonist treatment are distinct from the nonspecific effects of the drugs. This study provides fundamental insights that may contribute to our understanding of therapeutic mechanisms for fear memory disorders related to D2R in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exploring the perceptions of individuals with traumatic brain injury (TBI) towards their brain injury recovery across the continuum of care may offer insights to support engagement with rehabilitation services. Illness narratives are a potentially valuable avenue for examining perceptions of recovery that may influence engagement. AIMS: The aim of this study is to explore the perspective of individuals with severe TBI towards their communication, brain injury and recovery experiences at 6 months, 1 year and 2 years post‐injury. METHODS & PROCEDURES: Discourse samples were obtained from 12 participants with severe TBI at 6 months, 1 year and 2 years following injury. A standardised protocol was used to elicit responses relating to perceptions of communication, the brain injury narrative, and perceptions of recovery facilitators. A thematic analysis of the discourse samples was completed. OUTCOMES & RESULTS: Three overarching themes were identified: experiences of communication recovery are diverse (Theme 1), varied experiences of recovery and rehabilitation (Theme 2), and continuous and lifelong journey of recovery (Theme 3). Primary communication concerns included presence of anomia, dysarthria, conversational topic difficulties, impacts of fatigue and memory difficulties. Illness narratives revealed the importance of re‐establishing a sense of self and the perceived importance of a strong social network post‐injury. CONCLUSIONS & IMPLICATIONS: The varied nature of communication challenges and recovery after TBI highlights the need for holistic, multidisciplinary support as well as inclusion of family and friends in the recovery process. Social communication intervention is a perceived priority area for individuals with TBI. Illness narratives may also play a valuable role in therapy and help to shape post‐injury identity. Managing the impacts of fatigue on communication and encouraging individuals to take ownership over their recovery and treatment may also help to improve patient outcomes. Supporting individuals to construct positive brain injury narratives that reaffirm a sense of self and include perspectives of family and friends may offer a potential future avenue for rehabilitation. Tailored but flexible, team‐based service delivery models for individuals with TBI that span from acute to long‐term care are warranted. What this study adds?: What is already known on this subject: Communication recovery from traumatic brain injury (TBI) is complex and multifaceted. The perceptions of individuals with TBI toward their communication recovery is largely unknown. To establish rehabilitation services that meet the needs of these individuals, we need to understand how they experience communication recovery. What this paper adds to existing knowledge: Social communication interventions were perceived as a priority for intervention by individuals with TBI. Fatigue was identified as perceived barrier to communication recovery. Taking ownership over one's recovery process was revealed as a facilitator of recovery. Illness narratives were found to strengthen post‐injury identity over time. What are the potential or actual clinical implications of this work?: Speech pathologists should prioritise social communication interventions and fatigue management for communication. Facilitating ownership of the recovery process and offering long‐term supports are key aspects of treatment. Supporting positive illness narratives as part of treatment may facilitate post‐injury identity construction. [ABSTRACT FROM AUTHOR]

Aim: The three‐phase enriched environment (EE) intervention paradigm has been shown to improve learning and memory function after cerebral ischemia, but the neuronal mechanisms are still unclear. This study aimed to investigate the hippocampal–cortical connectivity and the metabolic interactions between neurons and astrocytes to elucidate the underlying mechanisms of EE‐induced memory improvement after stroke. Methods: Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) or sham surgery and housed in standard environment or EE for 30 days. Memory function was examined by Morris water maze (MWM) test. Magnetic resonance imaging (MRI) was conducted to detect the structural and functional changes. [18F]‐fluorodeoxyglucose (FDG) positron emission tomography (PET) was conducted to detect brain energy metabolism. PET‐based brain connectivity and network analysis was performed to study the changes of hippocampal–cortical connectivity. Astrocyte‐neuron metabolic coupling, including gap junction protein connexin 43 (Cx43), glucose transporters (GLUTs), and monocarboxylate transporters (MCTs), was detected by histological studies. Results: Our results showed EE promoted memory function improvement, protected structure integrity, and benefited energy metabolism after stroke. More importantly, EE intervention significantly increased functional connectivity between the hippocampus and peri‐hippocampal cortical regions, and specifically regulated the level of Cx43, GLUTs and MCTs in the hippocampus and cortex. Conclusions: Our results revealed the three‐phase enriched environment paradigm enhanced hippocampal–cortical connectivity plasticity and ameliorated post‐stroke memory deficits. These findings might provide some new clues for the development of EE and thus facilitate the clinical transformation of EE. [ABSTRACT FROM AUTHOR]

The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory models prior to the development of neuromuscular deficits that mirror human spastic paraplegia. Via pulldown-mass spectrometry analyses, we find that DDHD2 binds to the key synaptic protein STXBP1. Using STXBP1/2 knockout neurosecretory cells and a haploinsufficient STXBP1+/− mouse model of human early infantile encephalopathy associated with intellectual disability and motor dysfunction, we show that STXBP1 controls targeting of DDHD2 to the plasma membrane and generation of saturated FFAs in the brain. These findings suggest key roles for DDHD2 and STXBP1 in lipid metabolism and in the processes of synaptic plasticity, learning, and memory. Synopsis: The mechanisms by which neuronal activity affects lipid metabolism in the brain remain little understood. This study identifies the phospholipase A1 isoform DDHD2 and the key synaptic protein STXBP1 as important regulators of lipid metabolism in synaptic plasticity and long-term memory in mice. DDHD2 produces saturated free fatty acids (FFAs) in response to long-term memory acquisition. DDHD2 is targeted to the synapse via an interaction with STXBP1. Ablation of DDHD2 in mice diminishes saturated FFA responses to memory acquisition and leads to progressive neuromuscular and cognitive/memory deficits. STXBP1-haploinsufficient mice similarly exhibit reduced saturated FFAs. Ablation of phospholipase D1 has little effect on saturated FFAs and long-term memory. The phospholipase A1 isoform DDHD2 and the key synaptic protein STXBP1 control lipid metabolism in learning and long-term memory. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusions Tooth loss has various causes; however, its cause‐specific effects on health outcomes remain unclear. This study evaluated whether the association between past/current smoking and risk of dementia was mediated by tooth loss.This 9‐year‐follow‐up prospective cohort study targeted adults aged ≥65 years. Dementia incidence during 2013–2019, smoking status (never, past/current) in 2010 and the number of remaining teeth (≤19, ≥20) in 2013 were the outcome, exposure and mediator, respectively. We used causal mediation analysis to fit the Cox proportional hazards model and estimated the hazard ratio (HR) and 95% confidence interval (CI) of the natural indirect effect (NIE) of smoking on dementia incidence through tooth loss and their mediated proportions.Among 32,986 participants (mean age 72.6 years [1 SD = 5.4]; men 48.4%), the dementia incidence during follow‐up was 2.11/100 person‐years. Tooth loss significantly mediated the association between past/current smoking and dementia incidence; the NIE of fewer remaining teeth for past/current smokers compared to never smokers was HR = 1.03 (95% CI: 1.02–1.05), and the mediated proportion was 18.0%.Tooth loss significantly mediates the association between past/current smoking and an increased risk of dementia among older adults. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a common age‐related neurodegenerative brain disorder characterized by the impairment in memory and other cognitive functions. Although there is currently no successful pharmacotherapy for AD, researchers are continuously exploring the various pathogenesis of AD to develop potential therapeutic drugs. Of the multiple hypotheses for AD, the cholinergic and amyloid‐β (Aβ) hypothesis are the main targeting hypothesis for AD. Some researchers proposed that the symptoms involved in AD (loss of memory, cognitive impairment, and amnesia) are the main event linked to the cholinergic neurotransmitter (acetylcholine). Therefore, the development of AChE inhibitors to increase the level of ACh in the synaptic cleft can improve learning and memory in AD patients. Huprine X is a synthetic ChE inhibitor developed by the hybridization of Huperzine A and the synthetic drug tacrine. This review focuses on the last 10 year's literature search on huprine and its analogues for the treatment of AD. We expect that this review can be helpful for medicinal chemists, and neuro‐chemists to provide new ideas for the development of new drugs therapy for AD. [ABSTRACT FROM AUTHOR]

Summary: Targeted memory reactivation (TMR) during sleep enhances memory consolidation in young adults by modulating electrophysiological markers of neuroplasticity. Interestingly, older adults exhibit deficits in motor memory consolidation, an impairment that has been linked to age‐related degradations in the same sleep features sensitive to TMR. We hypothesised that TMR would enhance consolidation in older adults via the modulation of these markers. A total of 17 older participants were trained on a motor task involving two auditory‐cued sequences. During a post‐learning nap, two auditory cues were played: one associated to a learned (i.e., reactivated) sequence and one control. Performance during two delayed re‐tests did not differ between reactivated and non‐reactivated sequences. Moreover, both associated and control sounds modulated brain responses, yet there were no consistent differences between the auditory cue types. Our results collectively demonstrate that older adults do not benefit from specific reactivation of a motor memory trace by an associated auditory cue during post‐learning sleep. Based on previous research, it is possible that auditory stimulation during post‐learning sleep could have boosted motor memory consolidation in a non‐specific manner. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammation in which lipopolysaccharide (LPS) is released into circulation can cause cognitive dysfunction and we have previously shown that LPS impaired working memory (WM) which refers to the ability to guide incoming behavior by retrieving recently acquired information. However, the mechanism is not very clear, and currently, there is no approved strategy to improve inflammation‐induced WM deficit. Notably, epidemiological studies have demonstrated a lower occurrence rate of inflammatory‐related diseases in smoking patients, suggesting that inflammation‐induced WM impairment may be improved by nicotine treatment. Here, our object is to investigate the effect and potential mechanisms of acute and chronic nicotine treatment on LPS‐produced WM deficiency. Methods: Delayed alternation T‐maze task (DAT) was applied for evaluating WM which includes both the short‐term information storage and the ability to correct errors in adult male mice. Immunofluorescence staining and immunoblotting were used for assessing the levels and distribution of CREB‐regulated transcription coactivator 1 (CRTC1) and hyperpolarization‐activated cation channels 2 (HCN2) in the medial prefrontal cortex (mPFC) and hippocampus. Quantitative PCR and ELISA were employed for analyzing the mRNA and protein levels of TNF‐α and IL‐1β. Results: Our results revealed that administration of LPS (i.p.) at a dose of 0.5 mg/kg significantly produced WM impairment in the DAT task accompanied by an increase in IL‐1β and TNF‐α expression in the mPFC. Moreover, intra‐mPFC infusion of IL‐1Ra, an IL‐1 antagonist, markedly alleviated LPS‐induced WM deficiency. More important, chronic (2 weeks) but not acute nicotine (0.2 mg/kg, subcutaneous) treatment significantly alleviated LPS‐induced WM deficiency by upregulating CRTC1 and HCN2. Of note, intra‐mPFC infusion of HCN blocker ZD7288 produced significant WM deficiency. Conclusions: In summary, in this study, we show that chronic nicotine treatment ameliorates acute inflammation‐induced working memory deficiency by increasing CRTC1 and HCN2 in adult male mice. [ABSTRACT FROM AUTHOR]