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Dementia is a syndrome exhibiting progressive impairments on cognition and behavior beyond the normal course of aging, and Alzheimer's disease (AD) is one of the neurodegenerative diseases known to cause dementia. We investigated the effect of KGC07EH, the 30% ethanol extract of Euonymus hamiltonianus, against amyloid-β (Aβ) production and cognitive dysfunction in dementia models. KGC07EH was treated on Hela cells expressing the Swedish mutant form of amyloid precursor protein (APP), and the AD triple transgenic (3× TG) mice were given KGC07EH orally during 11–14 months of age (100 and 300 mg/kg/day). SH-SY5Y cell line was used to test KGC07EH on scopolamine-induced elevation of acetylcholinesterase (AChE) activity. ICR mice were intraperitoneally injected with scopolamine, and KGC07EH was administered orally (50, 100, and 200 mg/kg/day) for 4 weeks. KGC07EH treatment decreased Aβ, sAPPβ-sw, and sAPPβ-wt levels and APP protein expressions while sAPPα was increased in Swedish mutant–transfected HeLa cells. KGC07EH treatment also significantly reduced the accumulation of Aβ plaques and tau tangles in the brain of 3× TG mice as well as improving the cognitive function. In SH-SY5Y cells cultured with scopolamine, KGC07EH dose-dependently attenuated the increase of AChE activity. KGC07EH also improved scopolamine-induced learning and memory impairment in scopolamine-injected mice, and in their cerebral cortex and hippocampus, the expression levels of p-ERK, p-CREB, p-Akt, and BDNF were attenuated. KGC07EH inhibits APP processing and Aβ production both in vitro and in vivo, while enhancing acetylcholine signaling and cognitive dysfunction which are the major symptoms of dementia. [ABSTRACT FROM AUTHOR]

Background: Chronic Gulf War Illness (GWI) is characterized by cognitive and mood impairments, as well as persistent neuroinflammation and oxidative stress. This study aimed to investigate the efficacy of Epidiolex®, a Food and Drug Administration (FDA)-approved cannabidiol (CBD), in improving brain function in a rat model of chronic GWI. Methods: Six months after exposure to low doses of GWI-related chemicals [pyridostigmine bromide, N,N-diethyl-meta-toluamide (DEET), and permethrin (PER)] along with moderate stress, rats with chronic GWI were administered either vehicle (VEH) or CBD (20 mg/kg, oral) for 16 weeks. Neurobehavioral tests were conducted on 11 weeks after treatment initiation to evaluate the performance of rats in tasks related to associative recognition memory, object location memory, pattern separation, and sucrose preference. The effect of CBD on hyperalgesia was also examined. The brain tissues were processed for immunohistochemical and molecular studies following behavioral tests. Results: GWI rats treated with VEH exhibited impairments in all cognitive tasks and anhedonia, whereas CBD-treated GWI rats showed improvements in all cognitive tasks and no anhedonia. Additionally, CBD treatment alleviated hyperalgesia in GWI rats. Analysis of hippocampal tissues from VEH-treated rats revealed astrocyte hypertrophy and increased percentages of activated microglia presenting NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) complexes as well as elevated levels of proteins involved in NLRP3 inflammasome activation and Janus kinase/signal transducers and activators of the transcription (JAK/STAT) signaling. Furthermore, there were increased concentrations of proinflammatory and oxidative stress markers along with decreased neurogenesis. In contrast, the hippocampus from CBD-treated GWI rats displayed reduced levels of proteins mediating the activation of NLRP3 inflammasomes and JAK/STAT signaling, normalized concentrations of proinflammatory cytokines and oxidative stress markers, and improved neurogenesis. Notably, CBD treatment did not alter the concentration of endogenous cannabinoid anandamide in the hippocampus. Conclusions: The use of an FDA-approved CBD (Epidiolex®) has been shown to effectively alleviate cognitive and mood impairments as well as hyperalgesia associated with chronic GWI. Importantly, the improvements observed in rats with chronic GWI in this study were attributed to the ability of CBD to significantly suppress signaling pathways that perpetuate chronic neuroinflammation. [ABSTRACT FROM AUTHOR]

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Abstract The Astragalus grahamianus (AG) Royle ex. Benth is traditionally used for the treatment of various human disorders. The current research work is aimed to explore the neuroprotective anti-Parkinson effects of various fractions of Astragalus grahamianus (A. grahamianus). Fine powder of Astragalus grahamianus was extracted with 70% methanol and then fractionated with various solvents on the basis of polarity. Standard protocols were used to investigate the bioactive constituents present in the various plant fractions. In-vitro antioxidant potential of various fractions was checked using diverse free radicals. In-vivo rats model was used to determined the neuroprotective effects of methanol fraction of A. grahamianus. The results revealed that various fractions of A. grahamianus contain flavonoids, cardiac glycosides, steroids, gums, terpenes, proteins, and carbohydrates except chloroform fraction lake the presence of steroids, cardiac glycosides, gums and saponins, aqueous fraction of steroids, terpenoids, gums and saponins, n-Hexane fraction steroids, carbohydrates, alkaloids, gums and flavonoids. The highest amount of total phenolic contents was found in AGME (32.67 ± 2.3 mg GAE / g). The AGME also showed enhanced free radicals cations potential against DPPH, ABTS and H2O2, respectively. The correlation between AOA (antioxidant activity) and TPC (total phenolic contents) revealed to be substantial. Relative R2 values for ABTS, H2O2, and DPPH activity are 0.9974, 0.9845, and 0.9678, respectively. The in-vivo neuroprotective activities showed significant results. Our findings highlight significant antioxidant, and neuroprotective possessions of AGME attributed to powerful bioactive compounds.

Abstract Background Amyloid-β1-42 (Aβ1-42) plays an essential role in the development of the early stage of Alzheimer’s disease (AD). Asiatic acid (AA), an active compound in Centella asiatica L, exhibit neuroprotective properties in previous studies. Due to its low bioavailability, the nose-to-brain delivery technique was used to enhance AA penetration in the brain. In this study, AA was also loaded in solid lipid nanoparticles (SLNs) as a strategy to increase its absorption in the nasal cavity. Methods Memory impairment was induced via direct intracerebroventricular injection of Aβ1-42 oligomer into mouse brain. The neuroprotective effect and potential underlying mechanisms were investigated using several memory behavioral examinations and molecular techniques. Results The intranasal administration of AA in SLNs attenuated learning and memory impairment induced by Aβ1-42 in Morris water maze and novel object recognition tests. AA significantly inhibited tau hyperphosphorylation of pTau-S396 and pTau-T231 and prevented astrocyte reactivity and microglial activation in the hippocampus of Aβ1-42-treated mice. It is also decreased the high levels of IL-1β, TNF-α, and malondialdehyde (MDA) in mouse brain. Conclusions These results suggested that nose-to-brain delivery of AA in SLNs could be a promising strategy to treat the early stage of AD.

Diabetes-associated cognitive dysfunction is linked to chronic hyperglycemia, oxidative stress, inflammation, cholinergic dysfunction, and neuronal degeneration. We investigated the antidiabetic and neuroprotective activity of a mixture of Sclerocarya birrea, Nauclea latifolia, and Piper longum (SNP) in type 2 diabetic (T2D) rat model-induced memory impairment. Fructose (10%) and streptozotocin (35 mg/kg) were used to induce T2D in male Wistar rats. Diabetic animals received distilled water, metformin (200 mg/kg), or SNP mixture (75, 150, or 300 mg/kg). HPLC–MS profiling of the mixture was performed. Behavioral testing was conducted using the Y-maze, NORT, and Morris water mazes to assess learning and memory. Biochemical markers were evaluated, including carbohydrate metabolism, oxidative/nitrative stress, pro-inflammatory markers, and acetylcholinesterase activity. Histopathological examination of the pancreas and hippocampus was also performed. Fructose/STZ administration resulted in T2D, impaired short- and long-term memory, significantly increased oxidative/nitrative stress, pro-inflammatory cytokine levels, acetylcholinesterase activity (AChE), hippocampal neuronal loss and degeneration in CA1 and CA3 subfields, and neuronal vacuolation in DG. SNP mixture at 150 and 300 mg/kg significantly improved blood glucose and memory function in diabetic rats. The mixture reduced oxidative/nitrative stress and increased endogenous antioxidant levels. It also reduced serum IL-1β, INF-γ and TNF-α levels and ameliorated AChE activity. Histologically, SNP protected hippocampus neurons against T2D-induced neuronal necrosis and degeneration. We conclude that the aqueous extract of SNP mixture has antidiabetic and neuroprotective activities thanks to active metabolites identified in the plant mixture, which consequently normalized blood glucose, protected hippocampus neurons, and improved memory function in diabetic rats. [ABSTRACT FROM AUTHOR]

Background: Amyloid-β1-42 (Aβ1-42) plays an essential role in the development of the early stage of Alzheimer's disease (AD). Asiatic acid (AA), an active compound in Centella asiatica L, exhibit neuroprotective properties in previous studies. Due to its low bioavailability, the nose-to-brain delivery technique was used to enhance AA penetration in the brain. In this study, AA was also loaded in solid lipid nanoparticles (SLNs) as a strategy to increase its absorption in the nasal cavity. Methods: Memory impairment was induced via direct intracerebroventricular injection of Aβ1-42 oligomer into mouse brain. The neuroprotective effect and potential underlying mechanisms were investigated using several memory behavioral examinations and molecular techniques. Results: The intranasal administration of AA in SLNs attenuated learning and memory impairment induced by Aβ1-42 in Morris water maze and novel object recognition tests. AA significantly inhibited tau hyperphosphorylation of pTau-S396 and pTau-T231 and prevented astrocyte reactivity and microglial activation in the hippocampus of Aβ1-42-treated mice. It is also decreased the high levels of IL-1β, TNF-α, and malondialdehyde (MDA) in mouse brain. Conclusions: These results suggested that nose-to-brain delivery of AA in SLNs could be a promising strategy to treat the early stage of AD. [ABSTRACT FROM AUTHOR]

Cognitive impairment occurs in stroke and hip fracture patients. In mice, bone fracture (BF) exacerbates stroke-related neuronal damage and sensorimotor dysfunction. We hypothesize that BF exacerbates post-stroke cognitive impairment. Adult mice were randomly assigned into BF, stroke, BF+stroke (BF 6 h before stroke), and control (sham operated) groups. Memory function was evaluated weekly for eight weeks by Y maze test and at eight weeks post-surgeries by novel object recognition (NOR) test. The neuronal damage and inflammation in hippocampus were analyzed three days and eight weeks after the surgeries. In Y maze test, BF+stroke mice started making fewer alternations than controls two weeks after the surgeries. Significant difference between BF+stroke and stroke groups started at five weeks post-injury and continued to the end of the experiment. In NOR test, BF+stroke group spent less time on novel objective than that of other groups. Cx3cr1+ cells and CD68+ cells accumulated in the stratum lacunosum moleculare (SLM) on the ipsilateral side of stroke injury in stroke and BF+stroke mice. BF+stroke mice had a higher ratio of ipsilateral/contralateral Cx3cr1+ cell-density than that of stroke mice. Therefore, BF shortly before stroke exacerbates hippocampal inflammation and causes long-lasting memory dysfunction.

Abstract Aims Cognitive dysfunction occurs frequently in patients with heart failure (HF), but early detection remains challenging. Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker of cognitive decline in disorders of primary neurodegeneration such as Alzheimer's disease. We evaluated the utility of serum GFAP as a biomarker for cognitive dysfunction and structural brain damage in patients with stable chronic HF. Methods and results Using bead‐based single molecule immunoassays, we quantified serum levels of GFAP in patients with HF participating in the prospective Cognition.Matters‐HF study. Participants were extensively phenotyped, including cognitive testing of five separate domains and magnetic resonance imaging (MRI) of the brain. Univariable and multivariable models, also accounting for multiple testing, were run. One hundred and forty‐six chronic HF patients with a mean age of 63.8 ± 10.8 years were included (15.1% women). Serum GFAP levels (median 246 pg/mL, quartiles 165, 384 pg/mL; range 66 to 1512 pg/mL) did not differ between sexes. In the multivariable adjusted model, independent predictors of GFAP levels were age (T = 5.5; P

This study aimed to explore the mechanism underlying cognitive dysfunction mediated by the lateral hypothalamic area (LHA) in a hypothalamic-hippocampal circuit in rats with lesion-induced hypothalamic obesity (HO). The HO model was established by electrically lesioning the hypothalamic nuclei. The open field (OP) test, Morris water maze (MWM), novel object recognition (NOR), and novel object location memory (NLM) tests were used to evaluate changes in cognition due to alterations in the hypothalamic-hippocampal circuit. Western blotting, immunohistochemical staining, and cholera toxin subunit B conjugated with Alexa Fluor 488 (CTB488) reverse tracer technology were used to determine synaptophysin (SYN), postsynaptic density protein 95 (PSD95), ionized calcium binding adaptor molecule 1 (Iba1), neuronal nuclear protein (NeuN), and Caspase3 expression levels and the hypothalamic-hippocampal circuit. In HO rats, severe obesity was associated with cognitive dysfunction after the lesion of the hypothalamus. Furthermore, neuronal apoptosis and activated microglia in the downstream of the lesion area (the LHA) induced microglial infiltration into the intact hippocampus via the LHA-hippocampal circuit, and the synapses engulfment in the hippocampus may be the underlying mechanism by which the remodeled microglial mediates memory impairments in HO rats. The HO rats exhibited microglial infiltration and synapse loss into the hippocampus from the lesioned LHA via the hypothalamic-hippocampal circuit. The underlying mechanisms of memory function may be related to the circuit. [ABSTRACT FROM AUTHOR]

Aims: Cognitive dysfunction occurs frequently in patients with heart failure (HF), but early detection remains challenging. Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker of cognitive decline in disorders of primary neurodegeneration such as Alzheimer's disease. We evaluated the utility of serum GFAP as a biomarker for cognitive dysfunction and structural brain damage in patients with stable chronic HF. Methods and results: Using bead‐based single molecule immunoassays, we quantified serum levels of GFAP in patients with HF participating in the prospective Cognition.Matters‐HF study. Participants were extensively phenotyped, including cognitive testing of five separate domains and magnetic resonance imaging (MRI) of the brain. Univariable and multivariable models, also accounting for multiple testing, were run. One hundred and forty‐six chronic HF patients with a mean age of 63.8 ± 10.8 years were included (15.1% women). Serum GFAP levels (median 246 pg/mL, quartiles 165, 384 pg/mL; range 66 to 1512 pg/mL) did not differ between sexes. In the multivariable adjusted model, independent predictors of GFAP levels were age (T = 5.5; P < 0.001), smoking (T = 3.2; P = 0.002), estimated glomerular filtration rate (T = −4.7; P < 0.001), alanine aminotransferase (T = −2.1; P = 0.036), and the left atrial end‐systolic volume index (T = 3.4; P = 0.004). NT‐proBNP but not serum GFAP explained global cerebral atrophy beyond ageing. However, serum GFAP levels were associated with the cognitive domain visual/verbal memory (T = −3.0; P = 0.003) along with focal hippocampal atrophy (T = 2.3; P = 0.025). Conclusions: Serum GFAP levels are affected by age, smoking, and surrogates of the severity of HF. The association of GFAP with memory dysfunction suggests that astroglial pathologies, which evade detection by conventional MRI, may contribute to memory loss beyond ageing in patients with chronic HF. [ABSTRACT FROM AUTHOR]

Summary: Objective: Hippocampal dentation (HD) is a "toothlike" morphological feature observed on the inferior aspect of the human hippocampus. It has been found that HD varies dramatically in healthy adults and is positively associated with verbal and visual memory. In this work, we evaluate the loss of HD and its association with memory dysfunction in patients with temporal lobe epilepsy (TLE) who have hippocampal sclerosis (HS). Methods: Fifty‐eight unilateral HS patients with neuropsychological data were identified from a retrospective database. T1‐weighted magnetization‐prepared rapid acquisition gradient echo images (~1 mm resolution) were upsampled to.25 mm and were processed using ASHS software to obtain ultra‐high‐resolution segmentations and three‐dimensional renderings. Dentes were counted on the epileptic and contralateral sides, and associations were tested between dentation on the epileptic versus contralateral sides and measures of verbal and visuospatial memory with respect to the dominant versus nondominant hemisphere. Results: The median number of dentes in epileptic hippocampi was significantly lower than in contralateral hippocampi (p <.0001). Among cases with HS in the dominant hemisphere, verbal memory was significantly correlated with contralateral nondominant hemisphere dentation (r =.43, p =.04). Similarly, among cases of HS in the nondominant hemisphere, visual memory was significantly correlated with contralateral dominant hemisphere dentation (r =.48, p =.04). All other analyses were not significant. Significance: This is the first study characterizing dentation in TLE patients with HS and its memory correlates. There is marked loss of dentation in sclerotic hippocampi compared to the unaffected contralateral hippocampi. Material‐specific measures of memory performance are paradoxically correlated with dentation contralateral to the side with HS, suggesting that contralateral functional capacity explains some of the variation in memory across TLE patients. HD is an important variable to consider in understanding memory loss in TLE. [ABSTRACT FROM AUTHOR]

Background and Purpose: Patients with subcortical ischemic vascular disease (SIVD) suffer from memory disorders that are thought to be associated with the hippocampus. We aimed to explore changes in hippocampal subfields and the relationship between different hippocampal subfield volumes and different types of memory dysfunction in SIVD patients. Methods: A total of 77 SIVD patients with cognitive impairment (SIVD-CI, n = 39) or normal cognition (HC-SIVD, n = 38) and 41 matched healthy controls (HCs) were included in this study. Memory function was measured in all subjects, and structural magnetic resonance imaging (MRI) was performed. Then, the hippocampus was segmented and measured by FreeSurfer 6.0 software. One-way ANOVA was used to compare the volume of hippocampal subfields among the three groups while controlling for age, sex, education and intracranial volume (ICV). Then, post hoc tests were used to evaluate differences between each pair of groups. Finally, correlations between significantly different hippocampal subfield volumes and memory scores were tested in SIVD patients. Results: Almost all hippocampal subfields were significantly different among the three groups except for the bilateral hippocampal fissure (p = 0.366, p = 0.086, respectively.) and left parasubiculum (p = 0.166). Furthermore, the SIVD-CI patients showed smaller volumes in the right subiculum (p < 0.001), CA1 (p = 0.002), presubiculum (p = 0.002) and molecular layer of the hippocampus (p = 0.017) than the HC-SIVD patients. In addition, right subiculum volumes were positively related to Rey's Auditory Verbal Learning Test (RAVLT) word recognition (r = 0.230, p = 0.050), reverse digit span test (R-DST) (r = 0.326, p = 0.005) and Rey–Osterrieth Complex Figure Test (ROCF) immediate recall (r = 0.247, p = 0.035) scores, right CA1 volumes were positively correlated with RAVLT word recognition (r = 0.261, p = 0.026), and right presubiculum volumes showed positive relationships with R-DST (r = 0.254, p = 0.030) and ROCF immediate recall (r = 0.242, p = 0.039) scores. Conclusion: SIVD might lead to general reductions in volume in multiple hippocampal subfields. However, SIVD-CI patients showed atrophy in specific subfields, which might be associated with memory deficits. [ABSTRACT FROM AUTHOR]

Background and PurposePatients with subcortical ischemic vascular disease (SIVD) suffer from memory disorders that are thought to be associated with the hippocampus. We aimed to explore changes in hippocampal subfields and the relationship between different hippocampal subfield volumes and different types of memory dysfunction in SIVD patients.MethodsA total of 77 SIVD patients with cognitive impairment (SIVD-CI, n = 39) or normal cognition (HC-SIVD, n = 38) and 41 matched healthy controls (HCs) were included in this study. Memory function was measured in all subjects, and structural magnetic resonance imaging (MRI) was performed. Then, the hippocampus was segmented and measured by FreeSurfer 6.0 software. One-way ANOVA was used to compare the volume of hippocampal subfields among the three groups while controlling for age, sex, education and intracranial volume (ICV). Then, post hoc tests were used to evaluate differences between each pair of groups. Finally, correlations between significantly different hippocampal subfield volumes and memory scores were tested in SIVD patients.ResultsAlmost all hippocampal subfields were significantly different among the three groups except for the bilateral hippocampal fissure (p = 0.366, p = 0.086, respectively.) and left parasubiculum (p = 0.166). Furthermore, the SIVD-CI patients showed smaller volumes in the right subiculum (p < 0.001), CA1 (p = 0.002), presubiculum (p = 0.002) and molecular layer of the hippocampus (p = 0.017) than the HC-SIVD patients. In addition, right subiculum volumes were positively related to Rey’s Auditory Verbal Learning Test (RAVLT) word recognition (r = 0.230, p = 0.050), reverse digit span test (R-DST) (r = 0.326, p = 0.005) and Rey–Osterrieth Complex Figure Test (ROCF) immediate recall (r = 0.247, p = 0.035) scores, right CA1 volumes were positively correlated with RAVLT word recognition (r = 0.261, p = 0.026), and right presubiculum volumes showed positive relationships with R-DST (r = 0.254, p = 0.030) and ROCF immediate recall (r = 0.242, p = 0.039) scores.ConclusionSIVD might lead to general reductions in volume in multiple hippocampal subfields. However, SIVD-CI patients showed atrophy in specific subfields, which might be associated with memory deficits.

Impaired memory and cognitive function are the main features of Alzheimer's disease (AD). Unfortunately, currently available treatments cannot cure or delay AD progression. Moreover, the blood–brain barrier hampers effective delivery of treatment to the brain. Therefore, we aimed to evaluate the impact of intranasally delivered luteolin on AD using bile-salt-based nano-vesicles (bilosomes). Different bilosomes were prepared using 23-factorial design. The variables were defined by the concentration of surfactant, the molar ratio of cholesterol:phospholipid, and the concentration of bile salt. Results demonstrated optimized luteolin-loaded bilosomes with particle size (153.2 ± 0.98 nm), zeta potential (−42.8 ± 0.24 mV), entrapment efficiency% (70.4 ± 0.77%), and % drug released after 8 h (80.0 ± 1.10%). In vivo experiments were conducted on an AD mouse model via intracerebroventricular injection of 3 mg/kg streptozotocin. We conducted behavioral, biochemical marker, histological, and immune histochemistry assays after administering a luteolin suspension or luteolin bilosomes (50 mg/kg) intranasally for 21 consecutive days. Luteolin bilosomes improved short-term and long-term spatial memory. They also exhibited antioxidant properties and reduced levels of proinflammatory mediators. They also suppressed both amyloid β aggregation and hyperphosphorylated Tau protein levels in the hippocampus. In conclusion, luteolin bilosomes are an effective, safe, and non-invasive approach with superior cognitive function capabilities compared to luteolin suspension. [ABSTRACT FROM AUTHOR]

Objective: Epileptic seizures may cause skeletal muscle injury and memory dysfunctions. The present study was aimed to investigate the possible protective effects of exercising prior to seizure on seizure-induced oxidative injury in the skeletal muscle and brain. Materials and Methods: Sprague-Dawley male rats were assigned as non-exercise (n=16) and exercise groups (n=16). Following a 3-day exercise training, exercise protocol (30 min) was performed on a treadmill for 10 days, while control rats had no exercise. On the 11th day, the epileptic seizure was induced by a single intraperitoneal injection of pentylenetetrazol (PTZ) (45 mg/kg), while the control groups were injected with saline. Passive-avoidance test was initially performed before PTZ/saline injection and repeated 72 h later for the assessment of memory function. Brain and gastrocnemius muscles were taken for histological assessments and to determine the levels of malondialdehyde (MDA) and glutathione (GSH), myeloperoxidase (MPO) activity and luminal -- and lucigenin -- enhanced chemiluminescence levels. Results: Exercise training alone increased the formation of reactive oxygen species and elevated the antioxidant GSH capacity of the muscle tissue in the control rats, but these effects were not observed in the muscles of the exercised rats induced with a PTZ-seizure. On the other hand, short-term exercise alone had no effect on the basal oxidative parameters of the brain tissues. Prior exercise did not alter the average seizure scores or memory performances when compared to non-exercised groups, but suppressed the PTZ-induced elevations in MDA and chemiluminescence levels as well as MPO activity in the brain. Conclusion: A 10-day mild treadmill exercise reduced the oxidative brain damage due to a single seizure-induced excitotoxicity and exerted a preconditioning effect on the skeletal muscles exposed to tonic-clonic contractions. [ABSTRACT FROM AUTHOR]

Objective: Several lines of evidence demonstrated the role of anesthetic drugs in cognitive functions. Some anesthetic agents have been confirmed to be associated with long-term spatial memory and learning in aged animal models. Methods: C57BL/6 mice were divided into four different groups based on different concentrations of remimazolam treatments. Behavioral phenotype was observed by open field, rota rod, Morris water maze, and elevated plus maze test. Western blot was performed to see the expression pattern of different proteins. Confocal microscopy images were taken for neuronal and glial cells to see the effect of remimazolam on CNS cells. Results: We showed that remimazolam, a new anesthetic drug, impaired cognitive behavior. Repetitive doses of remimazolam have been found to induce neuronal loss with a significant change in morphology. Here, we showed that a higher concentration of remimazolam had a significant effect on CNS cell activation. We showed that remimazolam caused memory dysfunction by inducing neuronal apoptosis via glutamate excitotoxicity. It also exhibited amyloid β plaque in the brain via abnormal phosphorylation of tau protein. Remimazolam-mediated regulation of glial cells in mouse cortex was observed and robust activation of astrocytes and microglial cells was found. Finally, we assessed the behavioral phenotype of mice and found that treatment with remimazolam induced significant behavioral changes and memory dysfunction. Conclusions: This study provides insight into the mechanism of anesthetic drug-induced memory deficits and may help improve the therapeutic effects of anesthesia agents in clinical applications. [ABSTRACT FROM AUTHOR]

Abstract Background Bladder-related pain symptoms in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) are often accompanied by depression and memory deficits. Magnesium deficiency contributes to neuroinflammation and is associated with pain, depression, and memory deficits. Neuroinflammation is involved in the mechanical allodynia of cyclophosphamide (CYP)-induced cystitis. Magnesium-L-Threonate (L-TAMS) supplementation can attenuate neuroinflammation. This study aimed to determine whether and how L-TAMS influences mechanical allodynia and accompanying depressive symptoms and memory deficits in CYP-induced cystitis. Methods Injection of CYP (50 mg/kg, intraperitoneally, every 3 days for 3 doses) was used to establish a rat model of BPS/IC. L-TAMS was administered in drinking water (604 mg·kg−1·day−1). Mechanical allodynia in the lower abdomen was assessed with von Frey filaments using the up-down method. Forced swim test (FST) and sucrose preference test (SPT) were used to measure depressive-like behaviors. Novel object recognition test (NORT) was used to detect short-term memory function. Concentrations of Mg2+ in serum and cerebrospinal fluid (CSF) were measured by calmagite chronometry. Western blot and immunofluorescence staining measured the expression of tumor necrosis factor-α/nuclear factor-κB (TNF-α/NF-κB), interleukin-1β (IL-1β), and N-methyl-d-aspartate receptor type 2B subunit (NR2B) of the N-methyl-d-aspartate receptor in the L6–S1 spinal dorsal horn (SDH) and hippocampus. Results Free Mg2+ was reduced in the serum and CSF of the CYP-induced cystitis rats on days 8, 12, and 20 after the first CYP injection. Magnesium deficiency in the serum and CSF correlated with the mechanical withdrawal threshold, depressive-like behaviors, and short-term memory deficits (STMD). Oral application of L-TAMS prevented magnesium deficiency and attenuated mechanical allodynia (n = 14) and normalized depressive-like behaviors (n = 10) and STMD (n = 10). The upregulation of TNF-α/NF-κB signaling and IL-1β in the L6–S1 SDH or hippocampus was reversed by L-TAMS. The change in NR2B expression in the SDH and hippocampus in the cystitis model was normalized by L-TAMS. Conclusions Normalization of magnesium deficiency by L-TAMS attenuated mechanical allodynia, depressive-like behaviors, and STMD in the CYP-induced cystitis model via inhibition of TNF-α/NF-κВ signaling and normalization of NR2B expression. Our study provides evidence that L-TAMS may have therapeutic value for treating pain and comorbid depression or memory deficits in BPS/IC patients.

Sepsis-associated encephalopathy (SAE) is a frequent complication of severe systemic infection resulting in delirium, premature death, and long-term cognitive impairment. We closely mimicked SAE in a murine peritoneal contamination and infection (PCI) model. We found long-lasting synaptic pathology in the hippocampus including defective long-term synaptic plasticity, reduction of mature neuronal dendritic spines, and severely affected excitatory neurotransmission. Genes related to synaptic signaling, including the gene for activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and members of the transcription-regulatory EGR gene family, were downregulated. At the protein level, ARC expression and mitogen-activated protein kinase signaling in the brain were affected. For targeted rescue we used adeno-associated virus-mediated overexpression of ARC in the hippocampus in vivo. This recovered defective synaptic plasticity and improved memory dysfunction. Using the enriched environment paradigm as a non-invasive rescue intervention, we found improvement of defective long-term potentiation, memory, and anxiety. The beneficial effects of an enriched environment were accompanied by an increase in brain-derived neurotrophic factor (BDNF) and ARC expression in the hippocampus, suggesting that activation of the BDNF-TrkB pathway leads to restoration of the PCI-induced reduction of ARC. Collectively, our findings identify synaptic pathomechanisms underlying SAE and provide a conceptual approach to target SAE-induced synaptic dysfunction with potential therapeutic applications to patients with SAE., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Exposure to heat stress (HS) has adverse effects on brain function, leading to anxiety-like behavior and memory impairment. Sericin is a silk derived protein with various neurobiological activities. The present study has investigated the effects of sericin on anxiety and cognitive impairments, in HS-received mice. The adult male mice were exposed to HS (43 ºC, 15 min once a day for 14 days) and simultaneously treated with 100, 150, and 200 mg/kg/day of sericin through oral gavage. Elevated plus-maze and Lashley III Maze tests were used to evaluate anxiety and learning and memory, respectively. The hippocampal BAX, BCL-2, caspase3, caspase9 and heat-shock protein-70 (HSP-70) were evaluated by western blotting and oxidative stress markers including malondialdehyde (MDA), total antioxidant capacity (TAC), super oxide dismutase (SOD) as well as glutathione peroxidase (GPx) were evaluated by spectroscopy method. The serum was collected for the analysis of the corticosterone levels. Treatment with sericin in higher doses reversed anxiety-like behavior and cognitive deficit induced by HS. Moreover, heat exposure increased serum corticosterone, hippocampal MDA, apoptotic proteins and HSP-70 levels. Sericin administration decreased serum corticosterone and enhanced hippocampal antioxidant defense and attenuated apoptosis and HSP-70 levels. The results show that the protective effects of sericin against HS-mediated cognitive dysfunction and anxiety-like behavior is possibly through suppressing HSP-70, oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that memory deficit in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease with varying impairment of motor abilities and cognitive profile, may be independent from executive dysfunction. Our multimodal magnetic resonance imaging (MRI) approach, including resting state functional MRI (RS-fMRI), diffusion tensor imaging (DTI) and voxel-based morphometry (VBM), aimed to investigate structural and functional changes within and beyond the Papez circuit in non-demented ALS patients (n = 32) compared with healthy controls (HCs, n = 21), and whether these changes correlated with neuropsychological measures of verbal and non-verbal memory. We revealed a decreased functional connectivity between bilateral hippocampus, bilateral parahippocampal gyri and cerebellum in ALS patients compared with HCs. Between-group comparisons revealed white matter abnormalities in the genu and body of the corpus callosum and bilateral cortico-spinal tracts, superior longitudinal and uncinate fasciculi in ALS patients (p <.05, family-wise error corrected). Interestingly, changes of Digit Span forward performance were inversely related to RS-fMRI signal fluctuations in the cerebellum, while changes of both episodic and visual memory scores were inversely related to mean and radial diffusivity abnormalities in several WM fiber tracts, including middle cerebellar peduncles. Our findings revealed that ALS patients showed significant functional and structural connectivity changes across the regions comprising the Papez circuit, as well as more extended areas including cerebellum and frontal, temporal and parietal areas, supporting the theory of a multi-system pathology in ALS that spreads from cortical to subcortical structures. [ABSTRACT FROM AUTHOR]

Fluoride which is widespread in our environment and food due to its geological origin and industrial pollution has been identified as a developmental neurotoxicant. Gut-brain axis provides new insight into brain-derived injury. We previously found the psychoactive effects of a probiotic strain, Lactobacillus johnsonii BS15 against fluoride-induced memory dysfunction in mice by modulating the gut-brain axis. In this study, we aimed to detect the link between the reconstruction of gut microbiota and gut-brain axis through which probiotic alleviate fluoride-induced memory impairment. We also added an hour of water avoidance stress (WAS) before behavioral tests and sampling, aiming to demonstrate the preventive effects of the probiotic on fluoride-induced memory impairment after psychological stress. Mice were given fluoridated drinking water (sodium fluoride 100 ppm, corresponding to 37.8 ± 2.4 ppm F¯) for 70 days and administered with PBS or a probiotic strain, Lactobacillus johnsonii BS15 for 28 days prior to and throughout a 70 day exposure to sodium fluoride. Results showed that fluoride increases the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis and reduces the exploration ratio in novel object recognition (NOR) test and the spontaneous exploration during the T-maze test in mice following WAS, which were significantly improved by the probiotic. 16S rRNA sequencing showed a significant separation in ileal microbiota between the fluoride-treated mice and control mice. Lactobacillus was the main targeting bacteria and significantly reduced in fluoride-treated mice. BS15 reconstructed the fluoride-post microbiota and increased the relative abundance of Lactobacillus. D-lactate content and diamine oxidase (DAO) activity, two biomarkers of gut permeability were reduced in the serum of probiotic-inoculated mice. ZO-1, an intestinal tight junction protein was reduced by fluoride in mRNA, and its protein levels were increased by the probiotic treatment. Moreover, the hippocampus which is essential to learning and memory, down-regulated mRNA level of both the myelin-associated glycoprotein (MAG), and protein levels of brain-derived neurotrophic factor (BDNF), including the improvement of cAMP response element-binding protein (CREB) by BS15 in fluoride-exposed mice after WAS. Via spearman correlation analysis, Lactobacillus displayed significantly positive associations with the behavioral tests, levels of nerve development related factors, and intestinal tight junction proteins ZO-1, and negative association with TNF-α of the hippocampus, highlighting regulatory effects of gut bacteria on memory potential and gut barrier. These results suggested the psychoactive effects of BS15 on fluoride-induced memory dysfunction after psychological stress. In addition, there may be some correlations between fluoride-induced memory dysfunction and reconstruction of gut microbiota. Availability of data and materials: 16S rRNA sequencing reads have uploaded to NCBI. The accession code of 16S rRNA sequencing reads in the National Center for Biotechnology Information (NCBI) BioProject database: PRJNA660154.

Though the underlying mechanism remains elusive, a close relationship between psychological stress and intestinal inflammation has been widely accepted. Such a link is very important to set the basis for our understanding of the critical role of gut-brain axis (GBA) in homeostatic processes in health and disease. Probiotics that could confer benefits to mental health through GBA are referred to as “psychobiotics”. This study aimed to further determine whether a potential psychobiotic strain, Lactobacillus johnsonii BS15 could prevent memory dysfunction in mice induced by psychological stress through modulating the gut environment, including intestinal inflammation and permeability. Memory dysfunction in mice was induced by restraint stress (RS), one of the most commonly utilized models to mimic psychological stress. The mice were randomly categorized into three groups including no stress (NS), restraint stress (RS), and probiotic (RS-P) and administered with either phosphate buffered saline (NS and RS groups) or L. johnsonii BS15 (RS-P group) every day from day 1–28. From days 22–28, the mice in RS and RS-P groups were subjected to RS each day. Results revealed that BS15-pretreatment enhanced the performance of RS-induced mice during three different behavioral tests for memory ability and positively modulated the hypothalamic–pituitary–adrenal axis by attenuating the serum corticosterone level. In the hippocampus, L. johnsonii BS15 positively modulated the memory-related functional proteins related to synaptic plasticity, increased neurotransmitter levels, and prevented RS-induced oxidative stress and mitochondria-mediated apoptosis. In the intestines, L. johnsonii BS15 protected the RS-induced mice from damaged gut barrier by enhancing the mRNA levels of tight junction proteins and exerted beneficial effects on the anti-inflammatory cytokine levels reduced by RS. These findings provided more evidence to reveal the psychoactive effect of L. johnsonii BS15 against memory dysfunction in RS-induced mice by modulating intestinal inflammation and permeability.

Researchers are attempting to harness the advantages of the gut–brain axis to prevent neurocognitive disorders by enhancing intestinal health. In this study, four groups of ICR mice were orally gavaged with either phosphate-buffered saline (control and CW groups) or the probiotic strain Lactobacillus johnsonii BS15 (P and PW group; daily amounts of 2 × 108 colony-forming units) for 28 days. From days 22 to 28, the mice in the CW and PW groups were subjected to water-avoidance stress (WAS). The issue of whether psychological stress–induced memory dysfunction can be prevented via L. johnsonii BS15 pretreatment to modulate the gut–brain axis was investigated. Results show that L. johnsonii BS15 enhanced gut development by increasing villus height in the jejunum and ileum as well as villus height:crypt depth ratio in the ileum. L. johnsonii BS15 increased the activities of digestive enzymes, including trypsin and lipase in the jejunum and ileum. The intestinal goblet cell number was also increased by L. johnsonii BS15 pretreatment. Moreover, L. johnsonii BS15 balanced the gut microbiota by increasing the log10 DNA gene copies of Lactobacillus spp. and L. johnsonii and decreasing that of Enterobacteriaceae in the cecum. L. johnsonii BS15 also exerted preventive effects on intestinal permeability WAS by modulating diamine oxidase and D-lactate levels in the serum and mRNA expression levels of the tight junction proteins claudin-1, occludin, and ZO-1 in the jejunum and ileum. L. johnsonii BS15 pretreatment modulated inflammatory factors, specifically tumor necrosis factor-alpha, interferon-gamma, and interleukin-10. L. johnsonii BS15 pretreatment improved their performance in two behavioral tests, namely the novel object and T-maze tests. This result indicates that psychological stress–induced memory dysfunction possibly could be prevented through the gut–brain axis. In addition, L. johnsonii BS15 exerted beneficial effects on the hippocampus by modulating memory-related functional proteins, especially those related to synaptic plasticity, such as brain-derived neurotrophic factor and stem cell factor. Moreover, L. johnsonii BS15 recovered antioxidant capacity and exerted protective effects on mitochondrion-mediated apoptosis in the hippocampus. Collectively, the modulation of the gut–brain axis by L. johnsonii BS15 could be considered a promising non-invasive treatment modality for psychological stress–induced memory dysfunction.

Impaired memory and cognitive function are the main features of Alzheimer’s disease (AD). Unfortunately, currently available treatments cannot cure or delay AD progression. Moreover, the blood–brain barrier hampers effective delivery of treatment to the brain. Therefore, we aimed to evaluate the impact of intranasally delivered luteolin on AD using bile-salt-based nano-vesicles (bilosomes). Different bilosomes were prepared using 23-factorial design. The variables were defined by the concentration of surfactant, the molar ratio of cholesterol:phospholipid, and the concentration of bile salt. Results demonstrated optimized luteolin-loaded bilosomes with particle size (153.2 ± 0.98 nm), zeta potential (−42.8 ± 0.24 mV), entrapment efficiency% (70.4 ± 0.77%), and % drug released after 8 h (80.0 ± 1.10%). In vivo experiments were conducted on an AD mouse model via intracerebroventricular injection of 3 mg/kg streptozotocin. We conducted behavioral, biochemical marker, histological, and immune histochemistry assays after administering a luteolin suspension or luteolin bilosomes (50 mg/kg) intranasally for 21 consecutive days. Luteolin bilosomes improved short-term and long-term spatial memory. They also exhibited antioxidant properties and reduced levels of proinflammatory mediators. They also suppressed both amyloid β aggregation and hyperphosphorylated Tau protein levels in the hippocampus. In conclusion, luteolin bilosomes are an effective, safe, and non-invasive approach with superior cognitive function capabilities compared to luteolin suspension.

• OVA-sensitization induced cognitive deficits. • OVA-sensitization increased blood total and differential WBC and hippocampus TNF-α. • Exercise ameliorated these changes and increased the IL-10 level in the hippocampus. • Moderate can ameliorates cognitive dysfunction in asthma. The behavioral changes, including spatial learning and memory impairment as well as depressive- and anxiety-like behaviors in an animal model of asthma were demonstrated previously. On the other hand, there is increasing evidence that the anti-inflammatory actions of exercise are related to their neuroprotective properties against different insults in the brain. This study was aimed to explore the effects of moderate treadmill exercise on cognitive deficits and possible anti-inflammatory mechanisms in ovalbumin (OVA)-sensitized rats. The exercise groups were trained to run on the treadmill 30 min/day with an intensity of 12 m/min, 5 days/week for 4 weeks. Animals in the OVA groups were sensitized by two intraperitoneal (i.p.) injections of OVA (10 μg/injection) and challenged with OVA by inhalation during the treadmill running exercise period. Passive avoidance (PA) memory, levels of interleukin (IL)-10 and tumor necrosis factor (TNF)-α in the hippocampus, total and differential white blood cell (WBC) count in the blood as well as pathological changes of the lung were then evaluated. OVA-sensitization was resulted in cognitive deficits in the PA task, along with increased total and differential WBC in blood and TNF-α in the hippocampus. However, exercise ameliorated these changes and increased the IL-10 level in the hippocampus, suggesting that moderate treadmill exercise can improve memory impairment in OVA-sensitized rats due to its anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

La recherche internationale a exploré le fonctionnement post-traumatique à long terme des enfants et adolescents victimes de violence sexuelle, et en particulier, la perturbation de l'image du corps, les difficultés dans la construction identitaire et les dysfonctionnements mnésiques et dissociatifs. L'expert judiciaire chargé d'une mission d'expertise de crédibilité des présumées victimes doit tenir compte des effets des mécanismes de défense et des stratégies d'ajustement au niveau de la mémoire émotionnelle qui a tendance à déformer les faits dans l'intérêt de la survie psychique. Des procédures d'analyse du discours, comme la CBCA (Criteria-based content analysis), doivent donc être interprétées avec prudence, en tenant compte de tout le contexte clinique. We present the state-of-the-arts linked to long-term posttraumatic functioning of sexually abused children and adolescents, and especially their risk of disruption of body image, impairment of identity construction, dysfunction of memory and posttraumatic dissociation. The judicial expert who is in charge of an expertise of credibility with the alleged victim has to consider the effects of defence mechanisms and coping strategies on emotional memory, tending to distort facts in order to preserve psychic survival. Thus, current discourse analysis procedures, such as CBCA (Criteria-based content analysis), have to be interpreted with caution, taking into account the whole clinical context. [ABSTRACT FROM AUTHOR]

Researchers are attempting to harness the advantages of the gut–brain axis to prevent neurocognitive disorders by enhancing intestinal health. In this study, four groups of ICR mice were orally gavaged with either phosphate-buffered saline (control and CW groups) or the probiotic strain Lactobacillus johnsonii BS15 (P and PW group; daily amounts of 2 × 108 colony-forming units) for 28 days. From days 22 to 28, the mice in the CW and PW groups were subjected to water-avoidance stress (WAS). The issue of whether psychological stress–induced memory dysfunction can be prevented via L. johnsonii BS15 pretreatment to modulate the gut–brain axis was investigated. Results show that L. johnsonii BS15 enhanced gut development by increasing villus height in the jejunum and ileum as well as villus height:crypt depth ratio in the ileum. L. johnsonii BS15 increased the activities of digestive enzymes, including trypsin and lipase in the jejunum and ileum. The intestinal goblet cell number was also increased by L. johnsonii BS15 pretreatment. Moreover, L. johnsonii BS15 balanced the gut microbiota by increasing the log10 DNA gene copies of Lactobacillus spp. and L. johnsonii and decreasing that of Enterobacteriaceae in the cecum. L. johnsonii BS15 also exerted preventive effects on intestinal permeability WAS by modulating diamine oxidase and D-lactate levels in the serum and mRNA expression levels of the tight junction proteins claudin-1, occludin, and ZO-1 in the jejunum and ileum. L. johnsonii BS15 pretreatment modulated inflammatory factors, specifically tumor necrosis factor-alpha, interferon-gamma, and interleukin-10. L. johnsonii BS15 pretreatment improved their performance in two behavioral tests, namely the novel object and T-maze tests. This result indicates that psychological stress–induced memory dysfunction possibly could be prevented through the gut–brain axis. In addition, L. johnsonii BS15 exerted beneficial effects on the hippocampus by modulating memory-related functional proteins, especially those related to synaptic plasticity, such as brain-derived neurotrophic factor and stem cell factor. Moreover, L. johnsonii BS15 recovered antioxidant capacity and exerted protective effects on mitochondrion-mediated apoptosis in the hippocampus. Collectively, the modulation of the gut–brain axis by L. johnsonii BS15 could be considered a promising non-invasive treatment modality for psychological stress–induced memory dysfunction. [ABSTRACT FROM AUTHOR]

Background: Bladder-related pain symptoms in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) are often accompanied by depression and memory deficits. Magnesium deficiency contributes to neuroinflammation and is associated with pain, depression, and memory deficits. Neuroinflammation is involved in the mechanical allodynia of cyclophosphamide (CYP)-induced cystitis. Magnesium-L-Threonate (L-TAMS) supplementation can attenuate neuroinflammation. This study aimed to determine whether and how L-TAMS influences mechanical allodynia and accompanying depressive symptoms and memory deficits in CYP-induced cystitis.Methods: Injection of CYP (50 mg/kg, intraperitoneally, every 3 days for 3 doses) was used to establish a rat model of BPS/IC. L-TAMS was administered in drinking water (604 mg·kg-1·day-1). Mechanical allodynia in the lower abdomen was assessed with von Frey filaments using the up-down method. Forced swim test (FST) and sucrose preference test (SPT) were used to measure depressive-like behaviors. Novel object recognition test (NORT) was used to detect short-term memory function. Concentrations of Mg2+ in serum and cerebrospinal fluid (CSF) were measured by calmagite chronometry. Western blot and immunofluorescence staining measured the expression of tumor necrosis factor-α/nuclear factor-κB (TNF-α/NF-κB), interleukin-1β (IL-1β), and N-methyl-D-aspartate receptor type 2B subunit (NR2B) of the N-methyl-D-aspartate receptor in the L6-S1 spinal dorsal horn (SDH) and hippocampus.Results: Free Mg2+ was reduced in the serum and CSF of the CYP-induced cystitis rats on days 8, 12, and 20 after the first CYP injection. Magnesium deficiency in the serum and CSF correlated with the mechanical withdrawal threshold, depressive-like behaviors, and short-term memory deficits (STMD). Oral application of L-TAMS prevented magnesium deficiency and attenuated mechanical allodynia (n = 14) and normalized depressive-like behaviors (n = 10) and STMD (n = 10). The upregulation of TNF-α/NF-κB signaling and IL-1β in the L6-S1 SDH or hippocampus was reversed by L-TAMS. The change in NR2B expression in the SDH and hippocampus in the cystitis model was normalized by L-TAMS.Conclusions: Normalization of magnesium deficiency by L-TAMS attenuated mechanical allodynia, depressive-like behaviors, and STMD in the CYP-induced cystitis model via inhibition of TNF-α/NF-κВ signaling and normalization of NR2B expression. Our study provides evidence that L-TAMS may have therapeutic value for treating pain and comorbid depression or memory deficits in BPS/IC patients. [ABSTRACT FROM AUTHOR]

The nervous system is not just a target organ for synthetic steroids. It is also controlled in a certain manner by steroids synthesized de novo in the brain, at the level of both neurones and glial cells. The impressive recent number of literature studies, clearly demonstrates the presence of enzymes necessary for syntheses of central neurosteroids and also the mechanism by which they act. Neurosteroids play a considerable part as an endogenous modulator of brain function and behaviour processes, and the decrease of their concentration can be associated with the pathophysiology of different neurological diseases accompanied by cognitive disorders such as depression, anxiety, schizophrenia, Alzheimer disease. [ABSTRACT FROM AUTHOR]

Abstract Background Curcuma longa L. is a well-known medicinal plant that has been used for its anti-cancer, neuroprotective, and hepatoprotective effects. However, the neuroprotective effect of fermented C. longa (FCL) has not been reported. Therefore, in this study, the effectiveness of FCL for the regulation of memory dysfunction was investigated in two brain cell lines (rat glioma C6 and murine microglia BV2) and scopolamine-treated mice. Methods C. longa powder was fermented by 5% Lactobacillus plantarum K154 containing 2% (w/v) yeast extract at 30 °C for 72 h followed by sterilization at 121 °C for 15 min. The protective effects of fermented C. longa (FCL) on oxidative stress induced cell death were analyzed by MTT assay in C6 cells. The anti-inflammatory effects of FCL were investigated by measuring the production of nitric oxide (NO) and prostaglandin E2 (PGE2) as well as the expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated BV2 cells. The step-through passive avoidance test, Morris water maze test, acetylcholinesterase (AChE) activity, and expression of cAMP response element-binding protein (CREB) and brain-derived neurotropic factor (BDNF) were employed to determine the effects of FCL on scopolamine-induced memory deficit in mice. The contents of curcuminoids were analyzed through LC/MS. Results Pretreatment with FCL effectively prevented the cell death induced by oxidative stress in C6 cells. Moreover, FCL inhibited the production NO and PGE2 via the inhibition of iNOS and COX-2 expression in BV2 cells. FCL significantly attenuated scopolamine-induced memory impairment in mice and prevented scopolamine-induced AChE activity in the hippocampus. Additionally, FCL reversed the reduction of CREB and BDNF expression. The curcuminoids content in FCL was 1.44%. Conclusion FCL pretreatment could alleviate scopolamine-induced memory impairment in mice, as well as oxidative stress and inflammation in C6 and BV2 cells, respectively. Thus, FCL might be a useful material for preventing impairment of learning and memory.

Background: Epilepsy is a neurological condition in which recurrent seizures take place due to abnormal, excessive neural activity in the brain. This leads toinvoluntary change in the body movement or function. Studies have shown that seizures affect sensation, attention behavior and memory of an individual. Memory problems are very common and distressing to the patients. It is a matter of great concern as it affects their day to day functioning. The higher the frequency of seizures and/or the prolonged duration higher the dysfunction affecting quality of life of the individual. Aim: The study aimed at understanding memory dysfunction associated with primary generalized epilepsy. Methodology: The sample was selected using purposive sampling (N=30). Patients with primary generalized epilepsy were assessed on PGI memory scale (N=15) and were compared with control group (N=15). Results: The results revealed significant dysfunction of attention, concentration, and verbal retention in patients of primary generalized epilepsy. Remote memory and recognition on the other hand was found to be unaffected. Conclusion: The present study concludes that attention and concentration and short term memory is affected in patients withprimary generalized epilepsy.

Several mechanisms are involved in the loss of cellular integrity and tissue destructions in various brain regions during ischemic insult. The affected brain employs various self-repair mechanisms during the poststroke recovery. Therefore, the current study involves time course changes in different brain regions following ischemia in terms of inflammation, oxidative stress and apoptosis for which a bilateral common carotid arteries occlusion model was chosen. The development of oxidative stress was seen with a marked increase in ROS and NO levels with concomitant decrease in GSH levels and also the activities of anti-oxidant enzymes. These alterations were accompanied with decreased levels of neurotransmitters and motor and cognitive deficits at various time points. Increased expressions of various pro-inflammatory cytokines and a decline in BDNF levels in hippocampal regions on 7th day post ischemia, suggesting their role in its pathogenesis. The restoration of BDNF and neurotransmitter levels along with significant decline in inflammatory cytokine levels 14th day onwards following ischemia in hippocampus suggested poststroke recovery. The extent of neuronal damage was found to be increased significantly on 7th day post ischemia as indicated by TUNEL assay and hematoxylin and eosin staining depicting enhanced number of pyknotic neurons in cortical and hippocampal regions. Cortical regions of the ischemic brains were severely affected while hippocampal regions showed significant poststroke recovery, which might attributed to the normalization of BDNF and pro-inflammatory cytokine levels. In conclusion, the present study established the central role of BDNF and pro-inflammatory cytokines in the poststroke recovery. Also, the cortical and hippocampal regions were found to be more susceptible for ischemic injury. As our results indicated, full recovery after ischemic injury in different brain regions was not achieved, therefore further studies with long-term recovery time are required to be conducted. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Heat stress has harmful effects on the brain structure and synaptic density via induction of oxidative stress and neuroinflammation, which result in neuronal damage in the hippocampus and thereby cognitive impairments. In this study, we investigate the effect of Rosa canina treatment on cognitive function in heat stress‐exposed rats and its underlying mechanisms.What is the main finding and its importance?We show that R. canina improves cognitive deficits induced by heat stress by attenuation of oxidative stress and neuroinflammation and by upregulation of synaptic proteins in the hippocampus. The aim of the study was to evaluate the effects of aqueous methanolic extract of Rosa canina (RC) dried fruits on oxidative stress, inflammation, synaptic degeneration and memory dysfunction induced by heat stress (HS) in rats. Sixty adult male Wistar rats were randomly divided into five groups as follows: the control group received normal saline (NS); the HS group was exposed to heat stress (43°C) for 15 min once a day for 2 weeks; and HS+R groups were exposed to heat stress and received one of three doses (250, 500 or 1000 mg kg−1) of RC methanolic extract for 2 weeks. A passive avoidance test and a Y‐maze test were performed to assess learning and memory. The levels of reactive oxygen species were assessed. The serum cortisol concentration and hippocampal total antioxidant capacity, superoxide dismutase and glutathione peroxidase were also detected using spectrophotometry. The protein expressions of c‐Fos, heat‐shock protein‐70, tumour necrosis factor‐α, growth‐associated protein 43, post‐synaptic density‐95 and synaptophysin were evaluated in the hippocampal tissue. The results showed that RC significantly improved cognitive dysfunction induced by HS, which was accompanied by downregulation of tumour necrosis factor‐α and upregulation of growth‐associated protein 43 and synaptophysin proteins in the hippocampus of HS‐exposed rats. Furthermore, RC significantly attenuated serum cortisol concentrations and upregulated heat shock protein‐70 and c‐Fos in the hippocampus. In addition, the administration of RC attenuated reactive oxygen species levels and enhanced antioxidant defense in the hippocampus. These findings indicate that RC attenuated the deleterious effect of HS on cognition through its antioxidant properties and by enhancing synaptic function and plasticity. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is characterized with progressive memory loss and severe cognitive impairments, which affect everyday life and human health in the elderly. It is required that an effective and safe protective reagent against AD should be developed. It has been reported that humanin (HN) exerts neuroprotective effects against AD. In this study, we investigated the effect of a novel and more effective HN derivative, Colivelin (CLN) on AD. Methods: PDAPPV717I transgenic AD model mice (derived from parental C57/BL6 mice) were used in our study as AD model. Morris water maze test was used to test the memory impairment of AD mice and the levels of Aβ40 and Aβ42 were determined by an Elisa assay. We used an Immunohistochemistry and Immunofluorescence staining method to check the GFAP and MAP2 positive cells, and TUNEL to assess the apoptotic cells. Western blot assay was used to check the expression and phosphorylation level of p38. Results: We found that CLN improved the memory impairment induced by AD and reduced the deposit of Aβ40 and Aβ42. CLN also inhibited cell apoptosis and activation of caspase 3 in brain tissues of AD mice. Inflammation in AD mice was alleviated by CLN treatment, including the accumulation of GFAP positive cells and the inflammatory cytokines. With both structure of AGA-HNG and ANDF, CLN exhibited significantly stronger effects than synchronously administration of AGA-HNG and ADNF, suggesting CLN as a novel potential effective therapeutic reagent for AD patients. Finally, we found that CLN inhibited phosphorylation of p38 in AD mice and p38 inhibitor, SB203580 weakened the therapeutic effect of CLN. Conclusion: CLN effectively improved the memory dysfunction in PDAPP mice, and our data suggests CLN as a novel and effective reagent which may have great potentials in AD therapy.

Non-alcoholic fatty liver disease (NAFLD) and its complication non-alcoholic steatohepatitis (NASH) are important causes of liver disease worldwide. Recently, a significant association between these hepatic diseases and different central nervous system (CNS) disorders has been observed in an increasing number of patients. NAFLD-related CNS dysfunctions include cognitive impairment, hippocampal-dependent memory impairment, and mood imbalances (in particular, depression and anxiety). This review aims at summarizing the main correlations observed between NAFLD development and these CNS dysfunctions, focusing on the studies investigating the mechanism(s) involved in this association. Growing evidences point at cerebrovascular alteration, neuroinflammation, and brain insulin resistance as NAFLD/NASH-related CNS manifestations. Since the pharmacological options available for the management of these conditions are still limited, further studies are needed to unravel the mechanism(s) of NAFLD/NASH and their central manifestations and identify effective pharmacological targets.

We investigated the therapeutic effects and underlying brain functional network topology mechanisms of total salvianolic acid (TSA) treatment for memory dysfunction by using miR-30e overexpression-induced memory deficit in rat hippocampi. Model rats were developed by lentivirus vectors carrying miR-30e into bilateral hippocampus CA1 region through stereo-surgery. Two weeks after surgery, TSA (20 or 10 mg/mL/kg) or saline were administrated for 14 consecutive days. Memory function was assessed by behavioral tests (Y maze and Morris water maze [MWM]); resting-state functional MRI (RS-fMRI); and molecular alterations of BCL-2, UBC9, and Caspase-3 in the hippocampus CA1 region, as detected by immunohistochemistry. Compared to controls, model rats exhibited significantly impaired working and long-term memory in the Y maze and MWM tests (p < 0.01). The brain functional network topology analyzed based on RS-fMRI data demonstrated that miR-30e disturbed the global integration and segregation balance of the brain (p < 0.01), and reduced edge strength between CA1 and the posterior cingulate, temporal lobe, and thalamus (p < 0.05, false discovery rate corrected). At the molecular level, BCL-2 and UBC9 were downregulated, while Caspase-3 was upregulated (p < 0.01). After TSA (20 mg/mL/kg) treatment, the biomarkers for behavioral performance, global integration and segregation, edge strength, and expression levels of BCL-2, UBC9, and Caspase3 returned to normal levels. The correlation analyses of these results showed that global brain functional network topologic parameters can be intermediate biomarkers correlated with both behavioral changes and molecular alterations. This indicated that the effects of TSA were achieved by inhibiting apoptosis of CA1 neurons to improve global functional network topology.

We investigated the therapeutic effects and underlying brain functional network topology mechanisms of total salvianolic acid (TSA) treatment for memory dysfunction by using miR-30e overexpression-induced memory deficit in rat hippocampi. Model rats were developed by lentivirus vectors carrying miR-30e into bilateral hippocampus CA1 region through stereo-surgery. Two weeks after surgery, TSA (20 or 10 mg/mL/kg) or saline were administrated for 14 consecutive days. Memory function was assessed by behavioral tests (Y maze and Morris water maze [MWM]); resting-state functional MRI (RS-fMRI); and molecular alterations of BCL-2, UBC9, and Caspase-3 in the hippocampus CA1 region, as detected by immunohistochemistry. Compared to controls, model rats exhibited significantly impaired working and long-term memory in the Y maze and MWM tests (p < 0.01). The brain functional network topology analyzed based on RS-fMRI data demonstrated that miR-30e disturbed the global integration and segregation balance of the brain (p < 0.01), and reduced edge strength between CA1 and the posterior cingulate, temporal lobe, and thalamus (p < 0.05, false discovery rate corrected). At the molecular level, BCL-2 and UBC9 were downregulated, while Caspase-3 was upregulated (p < 0.01). After TSA (20 mg/mL/kg) treatment, the biomarkers for behavioral performance, global integration and segregation, edge strength, and expression levels of BCL-2, UBC9, and Caspase3 returned to normal levels. The correlation analyses of these results showed that global brain functional network topologic parameters can be intermediate biomarkers correlated with both behavioral changes and molecular alterations. This indicated that the effects of TSA were achieved by inhibiting apoptosis of CA1 neurons to improve global functional network topology. [ABSTRACT FROM AUTHOR]