A Novel Tetrapeptide Ala-Phe-Phe-Pro (AFFP) Derived from Antarctic Krill Prevents Scopolamine-Induced Memory Disorder by Balancing Lipid Metabolism of Mice Hippocampus.

Memory impairment is a serious problem with organismal aging and increased social pressure. The tetrapeptide Ala-Phe-Phe-Pro (AFFP) is a synthetic analogue of Antarctic krill derived from the memory-improving Antarctic krill peptide Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR) after digestion and absorption. The objective of this research was to assess the neuroprotective effects of AFFP by reducing oxidative stress and controlling lipid metabolism in the brains of mice with memory impairment caused by scopolamine. The 1H Nuclear magnetic resonance spectroscopy results showed that AFFP had three active hydrogen sites that could contribute to its antioxidant properties. The findings from in vivo tests demonstrated that AFFP greatly enhanced the mice's behavioral performance in the passive avoidance, novel object recognition, and eight-arm maze experiments. AFFP reduced oxidative stress by enhancing superoxide dismutase activity and malondialdehyde levels in mice serum, thereby decreasing reactive oxygen species level in the mice hippocampus. In addition, AFFP increased the unsaturated lipid content to balance the unsaturated lipid level against the neurotoxicity of the mice hippocampus. Our findings suggest that AFFP emerges as a potential dietary intervention for the prevention of memory impairment disorders.

Perinatal choline supplementation prevents learning and memory deficits and reduces brain amyloid Aß42 deposition in AppNL-G-F Alzheimer's disease model mice.

Alzheimer's disease (AD) is characterized by cognitive and memory impairments and neuropathological abnormalities. AD has no cure, inadequate treatment options, and a limited understanding of possible prevention measures. Previous studies have demonstrated that AD model mice that received a diet high in the essential nutrient choline had reduced amyloidosis, cholinergic deficits, and gliosis, and increased neurogenesis. In this study, we investigated the lifelong effects of perinatal choline supplementation on behavior, cognitive function, and amyloidosis in AppNL-G-F AD model mice. Pregnant and lactating mice were given a diet containing either 1.1 g/kg (control) or 5 g/kg (supplemented) of choline chloride until weaning and subsequently, all offspring received the control diet throughout their life. At 3, 6, 9, and 12 months of age, animals were behaviorally tested in the Open Field Test, Elevated Plus Maze, Barnes Maze, and in a contextual fear conditioning paradigm. Immunohistochemical analysis of Aß42 was also conducted on the brains of these mice. AppNL-G-F mice displayed hippocampal-dependent spatial learning deficits starting at 3-months-old that persisted until 12-months-old. These spatial learning deficits were fully prevented by perinatal choline supplementation at young ages (3 and 6 months) but not in older mice (12 months). AppNL-G-F mice also had impaired fearful learning and memory at 9- and 12-months-old that were diminished by choline supplementation. Perinatal choline supplementation reduced Aß42 deposition in the amygdala, cortex, and hippocampus of AppNL-G-F mice. Together, these results demonstrate that perinatal choline supplementation is capable of preventing cognitive deficits and dampening amyloidosis in AppNL-G-F mice and suggest that ensuring adequate choline consumption during early life may be a valuable method to prevent or reduce AD dementia and neuropathology.

Long-term calorie restriction prevented memory impairment in middle-aged male mice and increased a marker of DNA oxidative stress in hippocampal dentate gyrus.

Calorie restriction (CR) is a non-invasive and economic approachknown to increase healthspan and life expectancy, through a decrease in oxidative stress, an increase in neurotrophins, among other benefits. However, it is not clear whether its benefit could be noted earlier, as at the beginning of middle-age. Hence, weaimed to determine whether six months of long-term CR, from early adulthood to the beginning of middle age (10 months of age) could positively affect cognitive, neurochemical, and behavioral parameters. Male C57BL6/J mice were randomly distributed into Young Control (YC, ad libitum food), Old Control (OC, ad libitum food), and Old Restricted (OR, 30 % of caloric restriction) groups. To analyze the cognitive and behavioral aspects, the novel object recognition task (NOR), open field, and elevated plus maze tests were performed. In addition, immunohistochemistry targetingΔFosB (neuronal activity), brain-derived neurotrophic factor (BDNF) and the DNA oxidative damage (8OHdG) in hippocampal subfields CA1, CA2, CA3, and dentate gyrus (DG), and in basolateral amygdala and striatum were performed. Our results showed that long-term CR prevented short-term memory impairment related to aging and increased 8OHdG in hippocampal DG. BDNF was not involved in the effects of either age or CR on memory at middle-age, as it increased in CA3 of the OC group but was not altered in OR. Regarding anxiety-type behavior, no parameter showed differences between the groups. In conclusion, while the effects of long-term CR on anxiety-type behavior were inconclusive, it mitigated the memory deficit related to aging, which was accompanied by an increase in hippocampal 8OHdG in DG. Future studies should investigate whether the benefits of CR would remain if the restriction were interrupted after this long-term protocol.

Feeding metformin during pregnancy and lactation periods improved learning and memory impairment in the rat offspring exposed to febrile seizure: Role of oxidative stress and inflammatory response.

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.

Protective effect of Baoyuan Jieyu formula on long-term spaceflight composite stress-induced depressive-like behavior and memory deficits through regulation of Ca2+ channel currents.

Long-term spaceflight composite stress (LSCS) can cause adverse effects on human systems, especially the central nervous system. This study aimed to identify the underlying mechanisms of the protective effect of Baoyuan Jieyu Formula (BYJYF) on LSCS-induced depressive-like behavior and memory deficits. In this experiment, we simulated the real space station environment for a period of 42 days. Novel object recognition test and forced swimming test were used to assess the memory abilities and depression level of rats as well as test the therapeutic effects of BYJYF treatment. Results showed LSCS could induce depressive-like behavior and damage short-term memory in the behavioral level, and BYJYF could enhance the ability to resist LSCS. Meanwhile, LSCS increased the levels of CRH, ACTH, and CORT and induced HPA axis hyperactivity, which can be relieved by BYJYF. Further, we predicted and verified the potential signaling pathways of BYJYF. Results showed BYJYF may reverse the inhibition of LSCS on Ca2+ channel currents. And we also found that BYJYF may exert its medicinal effects via four main active components including saikosaponin A. Overall, BYJYF exhibited protective effects against LSCS-induced depressive-like behavior and memory deficits, which might be ascribed to the regulation of Ca2+ channel currents and four active components. And it might become a promising candidate medicine for diseases induced by LSCS.

Apple Pomace Extract Improves MK-801-Induced Memory Impairment in Mice.

Alzheimer's disease (AD) is a neurodegenerative disease that involves progressive cognitive decline accompanied by synaptic degeneration and impaired neurotransmission. Recent studies revealed that apple pomace, a waste byproduct of the apple processing industry, has beneficial health properties, but its potential to prevent and treat AD has not been determined. Herein, we examined the effects of apple pomace extract on N-methyl-D-aspartate receptor antagonist MK-801-induced memory impairment in mice. Repeated treatment with apple pomace extract for 7 days reversed the MK-801-induced impairment of associative memory and recognition memory. RNA sequencing revealed that repeated treatment with apple pomace extract altered the gene expression profile in the hippocampus of mice. Real-time PCR showed that apple pomace extract induced upregulation of the mRNA expression for Zfp125 and Gstp1. Furthermore, gene sets related to synapse and neurotransmission were upregulated by apple pomace extract. These findings indicate that apple pomace extract may be useful for the prevention and treatment of AD.

Intermittent working memory training during adulthood protects against age-related long-term spatial reference memory decline in rats.

Engagement in cognitive activity in adulthood is one of the factors that enable successful cognitive aging, both in humans and rodents. However, some studies emphasize that the beneficial effect on cognition of such an activity may reflect carry over from one test situation to another, including memory for procedural aspects of the behavioral tasks, and thus question whether this effect can be limited to the trained cognitive domain or whether it can be transferred to an untrained ones. In the current study, we assessed whether adulthood intermittent working memory training has beneficial effect on long-term memory of aged rats using two very different test situations. To this aim, rats trained in a delayed non-matching to position task in operant box at 3 and 15 months of age were tested in a place learning task in water maze when they were 24 months. The two tasks differ with regard to the cognitive domain but also in their spatial ability requirement and the nature of the reinforcer used. During the memory tests, accuracy of the platform search indicated age-related impairment only in the aged-untrained group. Thus, intermittent training during adult life in a task involving working memory protects aged animals from the deleterious effects of aging on spatial reference memory. This result highlights the long-term beneficial effects of training on a working memory task on an untrained cognitive domain.

Icariin rescues developmental BPA exposure induced spatial memory deficits in rats.

Bisphenol A (BPA) has been implicated in cognitive impairment. Icariin is the main active ingredient extracted from Epimedium Herb with protective function of nervous system. However, the potential therapeutic effects of Icariin on spatial memory deficits induced by developmental BPA exposure in Sprague-Dawley rats have not been investigated. This study investigated the therapeutic effect of Icariin (10 mg/kg/day, from postnatal day (PND) 21 to PND 60 by gavage) on spatial memory deficits in rat induced by developmental BPA exposure (1 mg/kg/day, from embryonic to PND 60), demonstrating that Icariin can markedly improve spatial memory in BPA-exposed rat. Furthermore, intra-gastric administration of Icariin could attenuate abnormal hippocampal cell dispersion and loss, improved the dendritic spine density and Nissl bodies. Moreover, Icariin reversed BPA induced reduction of frequency of miniature excitatory postsynaptic currents(mEPSC) and decrease of Vesicular glutamate transporter 1(VGlut1). Collectively, Icariin could effectively rescue BPA-induced spatial memory impairment in male rats by preventing cell loss and reduction of dendritic spines in the hippocampus. In addition, we also found that VGlut1 is a critical target in the repair of BPA-induced spatial memory by Icariin. Thus, Icariin may be a promising therapeutic agent to attenuate BPA-induced spatial memory deficits.

Treatment with the selective PDE4B inhibitor A-33 or PDE4D inhibitor zatolmilast prevents sleep deprivation-induced deficits in spatial pattern separation.

Sleep deprivation (SD) disrupts hippocampus-dependent memory, particularly in the dentate gyrus (DG) region, an area crucial for pattern separation. Previous research showed that non-selective phosphodiesterase type 4 (PDE4) inhibitors like roflumilast can alleviate these deficits. However, it remains unclear whether these outcomes are specific to a particular subfamily of PDE4. Hence, this study examined the specific impact of PDE4B inhibitor (A-33) and PDE4D inhibitor (zatolmilast) on spatial pattern separation in sleep deprived mice. Results demonstrated that SD impairs pattern separation, but both zatolmilast and A-33 alleviate these effects. However, A-33 impaired pattern separation in non-sleep deprived animals. The cognitive benefits of these inhibitors after SD may arise from alterations in relevant signaling pathways in the DG. This study provides initial evidence that inhibiting PDE4B or PDE4D holds promise for mitigating memory deficits due to SD.

Protective effect of vitamin D on learning and memory impairment in rats induced by high fructose corn syrup.

In our study, we aimed to investigate the negative effects of the prefrontal cortex (PFC)-associated impairment of cholinergic activity on memory and learning caused by high fructose corn syrup (HFCS) and the protective role of vitamin D in adolescent rats. Twenty-four animals were divided into three groups as control, HFCS group (11 % HFCS-55 solution, ad libitum) and HFCS+ Vit D (42 µg/kg/day). Elevated Plus Maze (EPM), Forced Swim Test (FST), and Morris Water Maze (MWM, performed from day 23) tests were applied to all animals. Fluid intake consumption of the rats was measured daily, weight gain and blood glucose were measured weekly. After 31 days of treatment, the rats were sacrificed and PFC tissue was removed for biochemical, histopathological and immunohistochemical analyses. In HFCS group, fluid consumption, blood glucose, malondialdehyde (MDA) levels, degenerative neuron count and choline acetyltransferase (ChAT) expression were significantly increased; superoxide dismutase (SOD), catalase (CAT) enzyme activity and brain-derived neurotrophic factor (BDNF) expression were significantly decreased. In addition, the time spent in the enclosed arm in EPM was increased, the immobility time in FST was, and the time spent in the target quadrant in MWM was significantly decreased. Vitamin D treatment reversed all these parameters. In conclusion, HFCS caused an increase in the number of degenerative neurons in the PFC, disrupted cholinergic activity and negatively affected learning-memory functions. Vitamin D, decreased the number of degenerative neurons, increased cholinergic activity and positively affected learning and memory performance. BRIEF SYNOPSIS: In this study, prefrontal cortex damage was investigated in adolescent rats fed high fructose corn syrup. The effect of vitamin D on prefrontal cortex damage was evaluated.

Effect of vitamin E on doxorubicin and paclitaxel-induced memory impairments in male rats.

PURPOSE: In addition to peripheral neuronal dysfunction, conventional chemotherapy can be associated with other neurological treatment-limiting adverse effects, including cognitive dysfunction, memory impairment, and anxiety, which are referred to as "chemobrain". This study aimed to investigate the effects of doxorubicin (DOX) and paclitaxel (PAC) on learning and memory in rats using radial arm water maze (RAWM) and investigated a potential beneficial effect of vitamin E (Vit. E). METHODS: Adult male rats were injected with four doses of 2 mg/kg/week DOX, or 2 mg/kg PAC every other day intraperitoneally. Vit. E was co-administered with these drugs in other groups to study its antioxidative effects. Using the RAWM, each rat was assessed for learning and memory performance through two sets of six trials separated by a 5-min rest period evaluating both short- and long-term effects on memory. RESULTS: There was no deficit in learning or long-term memory in both drug groups compared to control. However, rats in both drug groups made significantly more errors in all short-term memory trials. This effect was mitigated when Vit. E was co-administered with either drug. Moreover, PAC (but not DOX) induced hippocampal lipid peroxidation by increasing the levels of standard biomarker thiobarbituric acid reactive substances (TBARS). Interestingly, Vit. E prevented PAC-induced hippocampal oxidative stress. Furthermore, both DOX and PAC were correlated with reduction in Brain-Derived Neurotrophic Factor (BDNF) expression levels in the hippocampus, which was overcome by the co-administration of Vit. E. CONCLUSION: There is a potential role of Vit. E in alleviating short-term memory impairment in rats exposed to chemotherapy, possibly by reducing hippocampal oxidative stress and neurodegeneration.

Protective effects of alpha-lipoic acid on anxiety-like behavior, memory and prevention of hippocampal oxidative stress in methamphetamine-treated rats.

RATIONALE: Alpha-lipoic acid is an essential cofactor for aerobic metabolism and acts as a potent antioxidant in the body. It has been shown that acute exposure to methamphetamine induces oxidative stress, which is responsible for severe cognitive deficits in animals. The hippocampus plays a crucial role in the processing of memory and anxiety-like behavior. OBJECTIVES: In this study, preventive effect of the alpha-lipoic acid on memory impairment in methamphetamine-induced neurotoxicity was investigated. METHODS: Wistar male rats (200-220 g) were allocated to five groups (seven rats in each group): (1) saline + saline, (2) saline + vehicle (sunflower oil as alpha-lipoic acid solvent), (3) methamphetamine + vehicle, (4) methamphetamine + alpha-lipoic acid 10 mg/kg, and (5) methamphetamine + alpha-lipoic acid 40 mg/kg. Rats received intraperitoneal methamphetamine repeatedly (2 × 20 mg/kg, 2 h interval). Alpha-lipoic acid was injected 30 min, 24 h, and 48 h after the last injection of methamphetamine. The passive avoidance test and open field were used for evaluation of memory retrieval and anxiety, respectively. After behavioral test, rats were anesthetized, their brains were extracted, and after preparing hippocampal homogenates, malondialdehyde (MDA) level, catalase, and superoxide dismutase (SOD) activities were evaluated. RESULTS: Statistical analysis showed that injection of saline or sunflower oil had no significant effect on anxiety, memory, or oxidative stress markers. Methamphetamine induced memory impairment, increased anxiety-like behavior and MDA level, but it reduced catalase and SOD activity. Treatment with alpha-lipoic acid decreased MDA, increased catalase and SOD activity, and also prevented memory impairment and anxiety-like behavior. Our results showed that alpha-lipoic acid protected the hippocampus from oxidative stress by elevating SOD and CAT activities and reduced memory impairment following acute methamphetamine injection. These findings suggest that alpha-lipoic acid may have a protective effect against the adverse effects of methamphetamine exposure on the hippocampus. Therefore, the current data indicated that ALA can reduce oxidative stress predominantly by its antioxidant property.

Shark fish oil prevents scopolamine-induced memory impairment in an experimental model.

Fish oil has been known for its antioxidant, cardioprotective, anti-inflammatory, and neuroprotective characteristics due to the presence of polyunsaturated fatty acids (PUFAs) that are essential for optimal brain function and mental health. The present study investigated the effect of Carcharhinus Bleekeri (Shark Fish) oil on learning and memory functions in scopolamine-induced amnesia in rats. Locomotor and memory-enhancing activity in scopolamine-induced amnesic rats was investigated by assessing the open field and passive avoidance paradigm. Forty male Albino mice were divided into 4 equal groups (n = 10) as bellow: 1 - control (received 0.9% saline), 2 - SCOP (received scopolamine 2 mg/kg for 21 days), 3 - SCOP + SFO (received scopolamine and fish oil 5 mg/kg/ day for 21 days), 4 - SCOP + Donepezil groups (received 3 mg/kg/day for 21 days). SFO produced significant (P < 0.01) locomotor and memory-enhancing activities in open-field and passive avoidance paradigm models. Additionally, SFO restored the Acetylcholine (ACh) concentration in the hippocampus (p < 0.05) and remarkably prevented the degradation of monoamines. Histology of brain tissue showed marked cellular distortion in the scopolamine-treated group, while the SFO treatment restored distortion in the brain's hippocampus region. These results suggest that the SFO significantly ameliorates scopolamine-induced spatial memory impairment by attenuating the ACh and monoamine concentrations in the rat's hippocampus.

Reducing fear and avoidance of memory loss improves mood and social engagement in community-based older adults: a randomized trial.

BACKGROUND: Alzheimer's disease and related dementias (ADRD) are among the most feared age-related conditions. The aim of this study was to evaluate a brief psychological intervention to promote adaptive coping in older adults experiencing heightened fear of ADRD and investigate positive downstream effects on health-related secondary outcomes, including frequency of reported memory failures, psychosocial functioning, and quality of life. METHODS: Eighty-one older adults were recruited and randomized into REFRAME or active control intervention arms. Both groups received psycho-education and training in mindful monitoring of fears related to ADRD. The REFRAME group received an additional behavioral activation component intended to disrupt maladaptive avoidant coping (i.e., avoidance) strategies. Both groups completed 3-weeks of intervention exercises with accompanying questionnaires (baseline, mid- and post-intervention and 4-week follow-up). RESULTS: Adherence was strong (> 75%). We observed a significant reduction in ADRD-related fear and avoidance in both groups. Significant reductions were also observed for frequency of self-reported memory failures, anxiety, and depression. Depression was significantly reduced in the REFRAME group compared to the control group. Significant increases in participants' ability to participate in social activities and well-being were also observed. CONCLUSIONS: Findings suggest that a brief psychological intervention can mitigate ADRD-related fears and avoidant coping in older adults, and that benefits extend to broader health-related outcomes including anxiety, depression, social functioning, and well-being. Addressing ADRD-related fear has implications for healthy aging and risk reduction, as individuals may be more likely to engage in activities that are protective against ADRD but were previously avoided. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04821960 .

Omega-3 fatty acids prevent nicotine withdrawal-induced impairment of learning and memory via affecting oxidative status, inflammatory response, cholinergic activity, BDNF and amyloid-B in rat hippocampal tissues.

In the present study, the main objective was to reveal whether treatment by Omega-3 fatty acids could prevent the adverse effects of adolescent nicotine withdrawal on spatial and avoidance memory in male rats. For this purpose, Morris water maze and passive avoidance tests were performed on male Wistar rats and the hippocampal levels of oxidative stress markers, inflammatory indices, brain-derived neurotrophic factor, nitrite, amyloid-B and acetylcholinesterase (AChE) were measured. Moreover, density of dark neurons were assessed in CA1 and CA3 regions. Results showed that adolescent nicotine exposure followed by a period of drug cessation exacerbates the behavioral indices of learning and memory through affecting a variety of biochemical markers within the hippocampal tissues. These changes lead to elevation of oxidative and inflammatory markers, reduction of neurotrophic capacity and increased AChE activity in hippocampal tissues. In addition, it was observed that co-administration of nicotine with Omega-3 fatty acids significantly prevents nicotine withdrawal-induced adverse effects through restoration of the mentioned biochemical disturbances. Therefore, we suggest administration of Omega-3 fatty acids as a safe, inexpensive and effective therapeutic strategy for prevention of memory dysfunctions associated with nicotine abstinence during adolescence.

Pharmacological inhibition of plasminogen activator inhibitor-1 prevents memory deficits and reduces neuropathology in APP/PS1 mice.

RATIONALE: Extracellular proteolytic activity plays an important role in memory formation and the preservation of cognitive function. Previous studies have shown increased levels of plasminogen activator inhibitor-1 (PAI-1) in the brain of mouse models of Alzheimer's disease (AD) and plasma of AD patients, associated with memory and cognitive decline; however, the exact function of PAI-1 in AD onset and progression is largely unclear. OBJECTIVE: In this study, we evaluated a novel PAI-1 inhibitor, TM5A15, on its ability to prevent or reverse memory deficits and decrease Aß levels and plaque deposition in APP/PS1 mice. METHODS: We administered TM5A15 mixed in a chow diet to 3-month and 9-month-old APP/PS1 mice before and after neuropathological changes were distinguishable. We then evaluated the effects of TM5A15 on memory function and neuropathology at 9 months and 18 months of age. RESULTS: In the younger mice, 6 months of TM5A15 treatment protected against recognition and short-term working memory impairment. TM5A15 also decreased oligomer levels and amyloid plaques, and increased mBDNF expression in APP/PS1 mice at 9 months of age. In aged mice, 9 months of TM5A15 treatment did not significantly improve memory function nor decrease amyloid plaques. However, TM5A15 treatment showed a trend in decreasing oligomer levels in APP/PS1 mice at 18 months of age. CONCLUSION: Our results suggest that PAI-1 inhibition could improve memory function and reduce the accumulation of amyloid levels in APP/PS1 mice. Such effects are more prominent when TM5A15 is administered before advanced AD pathology and memory deficits occur.

Improvement of Cognitive Function by Fermented Panax ginseng C.A. Meyer Berries Extracts in an AF64A-Induced Memory Deficit Model.

This study investigated the potential therapeutic properties of fermented ginseng berry extract (GBE) for Alzheimer's disease (AD). Fermented GBE was examined for its ginsenoside content and physiological properties, which have been suggested to have neuroprotective effects and improve cognitive function. The results showed that fermented GBE contains high levels of major active ginsenosides and exhibits antioxidant and acetylcholinesterase inhibitory activities. Post-fermented GBE demonstrated therapeutic potential in AF64A-induced damaged neural stem cells and an animal model of AD. These findings suggest that fermented GBE may hold promise as a candidate for developing new therapeutic interventions for memory deficits and cognitive disorders associated with AD and other neurodegenerative conditions. However, further studies are needed to evaluate the safety, tolerability, and efficacy of fermented GBE in human subjects and to determine its clinical applications. In conclusion, our study provides evidence that fermented GBE has potential as a natural product for the prevention and treatment of AD. The high levels of active ginsenosides and antioxidant and acetylcholinesterase inhibitory activities of fermented GBE suggest that it may be a promising therapeutic agent for improving cognitive function and reducing neurodegeneration.

Beta-caryophyllene mitigates the cognitive impairment caused by repeated exposure to aspartame in rats: Putative role of BDNF-TrKB signaling pathway and acetylcholinesterase activity.

Aspartame (ASP) is a common sweetener, but studies show it can harm the nervous system, causing learning and memory deficits. ß-caryophyllene (BCP), a natural compound found in foods, including bread, coffee, alcoholic beverages, and spices, has already described as a neuroprotector agent. Remarkably, ASP and BCP are commonly consumed, including in the same meal. Therefore, considering that (a) the BCP displays plenty of beneficial effects; (b) the ASP toxicity; and (c) that they can be consumed in the same meal, this study sought to investigate if the BCP would mitigate the memory impairment induced by ASP in rats and investigate the involvement of the brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrKB) signaling pathway and acetylcholinesterase (AChE) activity. Young male Wistar rats received ASP (75 mg/kg; i.g.) and/or BCP (100 mg/kg; i.p.) once daily, for 14 days. At the end of the treatment, the animals were evaluated in the open field and object recognition tests. The cerebral cortex and hippocampus samples were collected for biochemical and molecular analyses. Results showed that the BCP effectively protected against the cognitive damage caused by ASP in short and long-term memories. In addition, BCP mitigated the increase in AChE activity caused by ASP. Molecular insights revealed augmented BDNF and TrKB levels in the hippocampus of rats treated with BCP, indicating greater activation of this pathway. In conclusion, BCP protected against ASP-induced memory impairment. AChE activity and the BDNF/TrkB signaling pathway seem to be potential targets of BCP modulatory role in this study.

Silymarin pretreatment protects against ethanol-induced memory impairment: Biochemical and histopathological evidence.

BACKGROUND: Ethanol (Eth.) abuse induces memory impairment. Oxidative damage and apoptosis are considered the likely causes of memory impairment. Silymarin (Sil.) is a flavonoid isolated from the plant Silymarin marianum (milk thistle). While studies have reported the neuroprotective effect of Sil. against neurodegenerative processes, the precise mechanism of action of Sil. in Eth.-induced memory impairment remains unclear. METHODS: Twenty-eight rats were equally divided into four groups: Control (saline 1 ml/rat); Sil. (200 mg/kg for 30 days); Eth. (2 g/kg/day for 30 days); and Sil. + Eth. Behavioral tests including inhibitory avoidance and open field were used to investigate memory and locomotion. Brain antioxidant parameters, including catalase, superoxide dismutase, total antioxidant capacity and total thiol group, plus oxidative parameters, including malondialdehyde and total oxidant status, followed by hippocampal apoptosis (Bax/Bcl2, cleaved caspase) and histopathological changes were evaluated in the groups. RESULTS: While the administration of Eth. impaired memory, Sil. significantly reversed Eth-induced memory deficits. Eth. administration also augmented brain oxidative and hippocampal apoptosis parameters. In contrast, a marked reduction in brain antioxidant and anti-apoptotic parameters was observed in the Eth. group. At the tissue level, hippocampal sections from Eth.-treated animals revealed severe neuronal damage. The administration of Sil. to Eth.-treated rats remarkably alleviated all the said Eth.-induced biochemical and histopathological effects. On the contrary, Sil. alone did not change the behavior and biochemical/molecular parameters. CONCLUSION: The memory-enhancing effect of Sil. in Eth.-induced demented rats may be partly mediated by the augmented antioxidant effects and amelioration of apoptotic and histopathological changes.

Agmatine prevents the memory impairment and the dysfunction of hippocampal GSK-3ß and ERK signaling induced by aluminum nanoparticle in mice.

The growing usage of aluminum nanoparticles (Al-NP) and their exposure may influence body function. Considering the proposed relationship between Al and the pathogenesis of Alzheimer's disease and the concern about the effect of this nanoparticle on brain health and cognitive function, the use of neuroprotective agents might be helpful. According to the reported neuroprotective effects of agmatine, in the present study, the possible protective effect of agmatine was assessed in mice model of Al-NP-induced memory impairment. In addition, due to the roles of hippocampal Glycogen synthase kinase-3 beta (GSK-3ß) and ERK signaling in memory and its disorders, these pathways were also investigated. Al-NP (10 mg/kg/p.o.) with/without agmatine (5 or 10 mg/kg/i.p.) was administered to adult male NMRI mice for 5 days. Novel object recognition (NOR) test session was used to assess cognitive function. Following the behavioral assessments, the hippocampi were used to determine the phosphorylated and total levels of GSK-3ß and ERK as well as GAPDH using western blot analysis. The results showed that Al-NP impaired NOR memory in mice while agmatine 10 mg/kg prevented the memory deficit induced by Al-NP. Furthermore, Al-NP activated GSK-3ß as well as ERK signals within the hippocampus while agmatine prevented the effects of Al-NP on GSK-3ß and ERK signals within the hippocampus. Besides supporting the neuroprotective effects of agmatine, these findings suggest the possibility of the connection of hippocampal GSK-3ß and ERK signaling in the neuroprotective effect of this polyamine against Al-NP.