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.

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.

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.

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.

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.

Lantana camara leaf extract ameliorates memory deficit and the neuroinflammation associated with scopolamine-induced Alzheimer's-like cognitive impairment in zebrafish and mice.

CONTEXT: Lantana camara Linn. (Verbenaceae) is used for improving memory in certain African societies. OBJECTIVE: This study investigated the effect of prophylactic treatment with hydroethanolic leaf extract of Lantana camara (LCE) on short-term memory deficit and neuroinflammation induced with scopolamine in zebrafish and mice. MATERIALS AND METHODS: Zebrafish (AB strain) and mice (ICR) were given donepezil (0.65 mg/kg, oral) and LCE (10, 30, 100 mg/kg, oral) for 7, and 10 days, respectively, before induction of cognitive impairment with scopolamine immersion (200 µM) and intraperitoneal injection (2 mg/kg), respectively. Spatial short-term memory was assessed in zebrafish using both Y- and T-mazes, whereas Y-maze was used in mice. Mice hippocampal and cortical tissues were analyzed for mRNA expression of proinflammatory genes (IL-1ß, IL-6, TNF-α, COX-2) using qRT-PCR. RESULTS: In the zebrafish Y-maze, LCE (10 and 100 mg/kg) increased time spent in the novel arm by 55.89 ± 5.70%, and 68.21 ± 2.75%, respectively, but not at 30 mg/kg. In the zebrafish T-maze, there was an increase in time spent in the food-containing arm at 30 (44.23 ± 2.13) and 100 mg/kg (52.30 ± 1.94). In the mouse Y-maze, spontaneous alternation increased by 52.89 ± 4.98% at only 10 mg/kg. LCE (10, 30, 100 mg/kg) inhibited proinflammatory gene (IL-1ß, IL-6, TNF-α, COX-2) mRNA expression, with the highest inhibitory effect on IL-6 in both the hippocampus (83.27 ± 2.49%; 100 mg/kg) and the cortex (98.74 ± 0.11%; 10 mg/kg). DISCUSSION AND CONCLUSION: LCE ameliorated scopolamine-induced AD in both zebrafish and mice.

Vitamin B12 administration prevents ethanol-induced learning and memory impairment through re-establishment of the brain oxidant/antioxidant balance, enhancement of BDNF and suppression of GFAP.

There are growing evidence indicating that the adolescent brain is persistently affected by the use of psychostimulant agents. In this regard, alcohol drinking has become rather common among the adolescents in many societies during the last decade. It is currently well known that long-term ethanol exposure deteriorates various cognitive functions such as learning and memory. Mechanistically, these adverse effects have been shown to be mediated by oxidative damage to central nervous system. On the other hand, Vit-B12 is known to improve cognitive performance by suppression of oxidative parameters. Thus, in the present study we aimed to test whether treatment by Vit-B12 could prevent ethanol-induced complications in mice using behavioral and biochemical methods. Different groups of male Syrian mice received ethanol, ethanol+Vit-B12, Vit-B12 alone, or saline during adolescence and then learning and memory functions were assessed by Morris water maze (MWM) and Passive Avoidance (PA) tests. Finally, mice were sacrificed for measurement of biochemical factors. Results indicated that, adolescent ethanol intake impairs learning and memory function through exacerbation of oxidative stress and Vit-B12 treatment improves these complications by re-establishment of oxidant/anti-oxidant balance in CNS. Moreover, we found that Vit-B12 prevents ethanol-induced reduction of BDNF and enhancement of GFAP and acetylcholinesterase (AChE) activity. In conclusion, it seems that Vit-B12 supplementation could be used as an effective therapeutic strategy to prevent learning and memory defects induced by chronic alcohol intake during adolescence.

Choline alleviated perinatal fluoride exposure-induced learning and memory impairment through α4ß2 nAChRs and α7 nAChRs in offspring mice.

Fluoride pollution is widely present in the living environment. As a critical period of brain development, the perinatal period is extremely vulnerable to fluoride. Studies have found that choline can protect the brain's memory and enhance the ability to focus. However, the effect of choline on perinatal fluoride-induced nerve damage remains unclear. Therefore, 32 Kunming newly conceived female mice and their offspring mice were randomly divided into control, NaF, LC + NaF, and HC + NaF groups, and the HE staining, Y-maze test, RT-PCR, western blotting, immunohistochemistry, etc. were used in this study. The results showed that fluoride decreased the brain organ coefficients and brain protein content (p < 0.05, p < 0.01), and caused histomorphological damage in the hippocampus and cortex, which suggested that fluoride affected the development of the brain and damaged the brain. Moreover, the results of the Y-maze test showed that fluoride increased the number of learning days, error reaction time, and total reaction time, and decreased the AchE activity in the brain (p < 0.05, p < 0.01), which indicated that fluoride reduced the learning and memory ability of the mice. Besides, the results showed that fluoride decreased the mRNA and protein expression levels of α4ß2 nAChRs and α7 nAChRs in the hippocampus and cortex (p < 0.05, p < 0.01). However, perinatal choline supplementation reversed the aforementioned fluoride-induced changes. In short, these results demonstrated that choline alleviated perinatal fluoride-induced learning and memory impairment, which will provide a rationale for the mitigation and prevention of fluoride-induced brain damage.

Treadmill running and Levisticum Officinale extract protect against LPS-induced memory deficits by modulating neurogenesis, neuroinflammation and oxidative stress.

Neuroinflammation plays an essential role in the pathogenesis of Alzheimer's disease. The preventive effect of physical exercise on attenuating neuroinflammation has not been completely defined. Levisticum officinale is known as a medicinal plant with antioxidant and anti-inflammatory properties. The current study was designed to investigate the neuroprotective impacts of treadmill running and Levisticum officinale on lipopolysaccharide (LPS)-induced learning and memory impairments and neuroinflammation in rats. Male Wistar rats ran on a treadmill and/or were pretreated with Levisticum officinale extract at a dose of 100 mg/kg for a week. Then, rats received intraperitoneal injection of LPS at a dose of 1 mg/kg. Treadmill running and/or treatment of extract lasted three more weeks. Behavioral, molecular, biochemical and immunohistochemical assessments were carried out after the end of the experiment. LPS administration resulted in spatial learning and memory impairments along with increased mRNA expression of interleukin-6 and malondialdehyde levels, as well as decreased superoxide dismutase activity and neurogenesis in the hippocampus. Moreover, treadmill running for four weeks, alone and in combination with Levisticum officinale extract attenuated spatial learning and memory deficits, decreased the mRNA expression of interleukin-6 and malondialdehyde levels, and enhanced superoxide dismutase activity and neurogenesis in the hippocampus. In conclusion, the advantageous effects of running exercise and Levisticum officinale extract on LPS-induced memory impairments are possibly due to the antioxidant and anti-inflammatory activity and enhancing neurogenesis.

Neuroprotective Effects of Poria cocos (Agaricomycetes) Essential Oil on Aß1-40-Induced Learning and Memory Deficit in Rats.

Alzheimer's disease (AD) is a neurodegenerative disease that has become a leading cause of death in recent years. The present study aimed to explore the possible prophylactic effects of Poria cocos essential oil (PCEO) against memory deficits in Aß rats. Adult male Wistar rats were given Aß1-42 via ICV injection. The effect of 30 d administration of PCEO by oral gavage was investigated. Novel object recognition (NOR) test, Morris water maze (MWM) test, and passive avoidance memory retention (PAM) task were performed. Aß decreased the cognitive memory in NOR, spatial memory in MWM, and passive avoidance memory in PAM tests. In contrast, PCEO improved learning and memory in the treated group. The PCEO treatment halts the activity of AChE in the hippocampus and cortex of the AD rats. The central neuronal degeneration in Aß-injected rats was not only ascertained by the histopathological changes but also confirmed indirectly by the concomitant increase in GFAP immunostaining. The beneficial effects in AD of increasing cellular GPx, GR, CAT, Na+ K+ ATPase and GST through the administration of PCEO may not only result in protection against neurodegeneration but also result in improvement in cognitive function. PCEO may be recommended as a prophylactic and/or adjunct medication for neurodegenerative diseases.

Thymus daenensis extract prevents scopolamine­induced memory impairment through declining oxidative stress in rats.

Memory and cognitive impairment induced by oxidative stress are among the main hallmarks of Alzheimer's disease's (AD) pathology. The present study aimed to investigate the potential neuroprotective effects of Thymus daenensis (T. daenensis) extract against scopolamine­induced memory impairment and oxidative stress in rats. T. daenensis, widely distributed in Iran and Europe, is known to be a rich source of natural antioxidants and has been traditionally used for various medical purposes. The present study investigated the post­treatment effects of T. daenensis on learning and memory functions, antioxidant cellular defense, and oxidative stress using the scopolamine rat model of AD. The experiments were performed by intraperitoneal injection of scopolamine for 10 consecutive days in Wistar male rats (180-220 g). Additionally, the animals received T. daenensis extract (50­200 mg/kg) by gavage for 14 consecutive days after induction of memory impairment. The animals were divided into 8 groups, namely: control, 200 mg/kg of T. daenensis extract (D200), donepezil (DON), scopolamine (ALZ), ALZ animals treated with different doses of the extract (ALZ+D50 or 100 or 200 mg/kg) and ALZ animals treated with (ALZ+DON). The animals were then subjected to the Morris water maze (MWM) paradigm as a standard criterion for memory function assessment, and after extracting the brain tissues, the related biochemical oxidative stress parameters were determined in the brain. Our results indicated that T. daenensis extract significantly improved animals' performance in the MWM while significantly reducing oxidative stress and antioxidant imbalance. Furthermore, the extract did not show hepatotoxic effects on treated animals. In addition, the extract treatment significantly decreased both cellular malondialdehyde (MDA) and protein carbonyl (PCO) content while conversely increasing the total reduced glutathione (GSH) content and also the levels of total and endogenous antioxidants in the ferric reducing antioxidant power (FRAP) assay. It seems that the administration of T. daenensis significantly improved both cellular biochemical aspects and memory performance in animal models. Conclusively, it could be beneficial for scopolamine­induced neurotoxicity.

Brassica rapa L. (Tibetan turnip) prevents sleep-deprivation induced cognitive deficits via the inhibition of neuroinflammation and mitochondrial depolarization.

Brassica rapa L., an edible, feeding and medicinal plant cultivated on the Tibetan plateau with altitudes above 3800 m, has several pharmacological effects. However, its therapeutic effects against memory impairment and central fatigue have yet to be conclusively established. In this study, the Y-maze and Morris water maze tasks revealed that Brassica rapa L. aqueous extract (BE) significantly ameliorated cognitive deficits of sleep deprivation (SD)-treated mice. Moreover, BE treatment partially alleviated SD-induced reductions in the levels of peripheral energy metabolism, and significantly decreased inflammatory factor levels in serum and hippocampus. In addition, BE treatment significantly relieved central fatigue and stabilized the excitability as well as activities of neurons by regulating the levels of hypothalamus tryptophan metabolites and striatum neurotransmitters. The neuroprotective effects of BE were also confirmed using glutamate-treated HT22 cells, whereby BE pretreatment significantly attenuated intracellular ROS production and mitochondrial depolarization via adenosine 5'-monophosphate activated protein kinase/peroxisome proliferators-activated receptors (AMPK/PPAR-γ) signaling pathways. Thus, BE might probably prevent SD-induced learning and memory deficits by inhibiting neuroinflammation and restoring mitochondrial energy metabolism in the hippocampus. These findings imply that BE is a potential complementary therapy for those suffering from deficient sleep or neurometabolic disorders, although this needs verification by prospective clinical studies.

Protective Effect of Ginsenosides from Stems and Leaves of Panax ginseng against Scopolamine-Induced Memory Damage via Multiple Molecular Mechanisms.

Although growing evidence has shown that ginsenosides from stems and leaves of Panax ginseng (GSLS) exercise a protective impact on the central nervous system, in the model of memory damage induced by scopolamine, it is still rarely reported. Thus, the mechanism of action needs to be further explored. This study was to investigate the effect of GSLS on scopolamine (SCOP)-induced memory damage and the underlying mechanism. Male ICR mice were treated with SCOP (3 mg/kg) for 7 days, with or without GSLS (75 and 150 mg/kg) treatment for 14 days. After GSLS treatment, the memory damage induced by SCOP was significantly ameliorated as shown by the improvement of cholinergic function (AChE and ChAT), brain tissue hippocampus morphology (H&E staining), and oxidative stress (MDA, GSH, and NO). Meanwhile, immunohistochemical assay suggested that GSLS increased the expression of brain-derived neurotrophic factor (BDNF) and Tyrosine Kinase receptor B (TrkB). Further mechanism research indicated that GSLS inhibited the Tau hyperphosphorylation and cell apoptosis by regulating the PI3K/AKT pathway and inhibited neuroinflammation by regulating the NF-κB pathway, thereby exerting a cognitive impairment improvement effect. This work suggested that GSLS could protect against SCOP-induced memory defects possibly through inhibiting oxidative stress, inhibiting neuroinflammation and cell apoptosis.

Dietary omega-3 fatty acids prevent neonatal seizure-induced early alterations in the hippocampal glutamatergic system and memory deficits in adulthood.

OBJECTIVE: We investigated the influence of dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) on glutamatergic system modulation after a single episode of neonatal seizures and their possible effects on seizure-induced long-lasting behavioral deficits. METHODS: Male Wistar rats receiving an omega-3 diet (n-3) or an n-3 deficient diet (D) from the prenatal period were subjected to a kainate-induced seizure model at P7. Glutamate transporter activity and immunocontents (GLT-1 and GLAST) were assessed in the hippocampus at 12, 24, and 48 h after the seizure episode. Fluorescence intensity for glial cells (GFAP) and neurons (NeuN) was assessed 24 h after seizure in the hippocampus. Behavioral analysis (elevated-plus maze and inhibitory avoidance memory task) was performed at 60 days of age. RESULTS: The D group showed a decrease in glutamate uptake 24 h after seizure. In this group only, the GLT1 content increased at 12 h, followed by a decrease at 24 h. GLAST increased up to 24 h after seizure. GFAP fluorescence was higher, and NeuN fluorescence decreased, in the D group independent of seizures. In adulthood, the D group presented memory deficits independent of seizures, but short-term memory (1.5 h after a training session) was abolished in the D group treated with kainate. SIGNIFICANCE: N-3 PUFA positively influenced the glutamatergic system during seizure and prevented seizure-related memory deficits in adulthood.

Combination of tea polyphenols and proanthocyanidins prevents menopause-related memory decline in rats via increased hippocampal synaptic plasticity by inhibiting p38 MAPK and TNF-α pathway.

OBJECTIVE: Many studies have examined the beneficial effects of tea polyphenols (TP) and proanthocyanidins (PC) on the memory impairment in different animal models. However, the combined effects of them on synaptic, memory dysfunction and molecular mechanisms have been poorly studied, especially in the menopause-related memory decline in rats. METHODS: In this rat study, TP and PC were used to investigate their protective effects on memory decline caused by inflammation. We characterized the learning and memory abilities, synaptic plasticity, AMPAR, phosphorylation of the p38 protein, TNF-ɑ, structural synaptic plasticity-related indicators in the hippocampus. RESULTS: The results showed that deficits of learning and memory in OVX + D-gal rats, which was accompanied by dendrites and synaptic morphology damage, and increased expression of Aß1-42 and inflammation. The beneficial effects of TP and PC treatment were found to prevent memory loss and significantly improve synaptic structure and functional plasticity. TP+PC combination shows more obvious advantages than intervention alone. TP and PC treatment improved behavioral performance, the hippocampal LTP damage and the shape and number of dendrites, dendritic spines and synapses, reduced the burden of Aß and decreased the inflammation in hippocampus. In addition, TP and PC treatment decreased the expressions of Iba-1, TNF-α, TNFR1, and TRAF2. CONCLUSIONS: These results provided a novel evidence TP combined with PC inhibits p38 MAPK pathway, suppresses the inflammation in hippocampus, and increase the externalization of AMPAR, which may be one of the mechanisms to improve synaptic plasticity and memory in the menopause-related memory decline rats.

A novel nutritional mixture, MBN, prevents memory impairment via inhibiting NLRP3 inflammasome formation in 5xFAD transgenic mice.

OBJECTIVES: Amyloid beta (Aß)-induced abnormal neuroinflammation is recognized as a major pathological factor of Alzheimer's disease (AD), which results in memory impairment. Inhibition of excessive neuroinflammation mediated by Aß is considered a promising strategy to ameliorate AD symptoms. To regulate the inflammatory response, nutritional and dietary supplements have been used for centuries. Based on this idea, we investigated whether MBN, a novel nutritional mixture including cassia bark, turmeric root, and ginkgo leaf, can prevent AD progression through neuroinflammatory regulation. METHODS: MBN (10, 30, or 100 µg/ml) and Aß1-42 monomer were incubated together, and the degree of Aß aggregation was measured using Thioflavin T assay. The effects of MBN on Aß pathology in vivo were evaluated by orally administering MBN (40 mg/kg/day for 16 weeks) to five familial AD (5xFAD) mice. RESULTS: We found that treatment with MBN inhibited Aß aggregation in vitro. Next, MBN treatment significantly inhibited the activation of microglia induced by aggregated Aß in 5xFAD mice. Caspase-1 activation, which plays an important role in the maturation of interleukin-1ß, was markedly reduced by MBN. We also found that oral administration of MBN in 5xFAD mice alleviated memory decline. Taken together, our findings demonstrate that MBN suppresses neuroinflammation by downregulating the caspase-1 expression, thereby ameliorating memory impairment in 5xFAD mice. DISCUSSION: Based on these results, we suggest that MBN may be a preventive and therapeutic supplement for AD through the regulation of neuroinflammation.

Evaluating the effect of selenium on spatial memory impairment induced by sleep deprivation.

Sleep deprivation (SD) impairs memory due to disturbing oxidative stress parameters. Selenium is a main component of several antioxidant enzymes and provides a neuroprotective effect. The present study aimed to investigate the potential neuroprotective effect of chronic selenium administration on cognitive impairments induced by chronic SD. Adult male Wister rats were randomly assigned into five groups (n = 12/group). The SD was induced in rats using modified multiple platform model. Selenium (6 µg/kg of animal's body weight) was administered to rats via oral gavage for 6 weeks. The spatial learning and memory were assessed using the radial arm water maze (RAWM). Moreover, we measured the levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and GSH/GSSG, catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS) and brain derived neurotrophic factor (BDNF) in the hippocampus. The results indicate that short- and long-term memory were impaired by chronic sleep deprivation (P < 0.05), while selenium administration prevented this effect. Moreover, selenium normalized antioxidants activities which were reduced by SD such as: catalase (P < 0.05), and SOD (P < 0.05), and significantly enhanced the ratio of GSH/GSSG in sleep-deprived rats (P < 0.05), without significant alteration of BDNF (P > 0.05), GSH (P > 0.05), or TBARS levels (P > 0.05). In conclusion, chronic SD induced memory impairment, and chronic treatment with selenium prevented this impairment by normalizing antioxidant enzymes activities in the hippocampus.

Moringa oleifera-supplemented diet protect against cortico-hippocampal neuronal degeneration in scopolamine-induced spatial memory deficit in mice: role of oxido-inflammatory and cholinergic neurotransmission pathway.

The therapeutic and pharmacological management of Alzheimer's disease (AD) is generally considered a major concern in ethnomedicine. Moreover, plant-based foods containing flavonoids were previously reported to show neuroprotective effects by modulating self-aggregation of amyloid-ß (Aß)/or tau peptide into oligomers and fibrils, associated with the pathogenesis of AD. This study investigated the impact of Moringa oleifera-supplemented diet (MO-SD) in scopolamine-induced spatial memory deficit in mice. Mice were partitioned into two phases with five groups each (n=6) and pretreated intraperitoneally with scopolamine (1 mg/kg) prior the daily oral administration of MO-SD (1 %, 5 % and 10 %) for 7 and 14 days. Spatial memory function was assessed using the Morris water maze (MWM) test. Thereafter, markers of cholinergic system inhibition (Acetylcholinesterase; AChE) and oxido-inflammatory stress (Malonaldehyde, MDA; Nitrite; Superoxide Dismutase, SOD; Tumor necrosis factor-alpha, TNF-α) and histo-morphology of the cortico-hippocampal neuron were measured. The scopolamine treatment led to loss of spatial memory function in mice spatial exploration of the escape platform in the MWM test. Meanwhile, treatment with MO-SD attenuated loss of spatial memory function via significant decrease in escape latency, significant increase in the frequency of cross with time spent in the platform quadrant. Furthermore, scopolamine treatment altered the endogenous antioxidants and pro-inflammatory mediators, elevated acetylcholinesterase activity and promoted chromatolysis of the cortico-hippocampal neuron. However, MO-SD significantly ameliorated oxido-inflammatory stress, restored cholinergic transmission via acetylcholinesterase inhibition and maintains neuronal integrity in the mice brain at both phases. These results suggest that Moringa oleifera-supplemented diet may serve a potential therapeutic and possible pharmacological macromolecule for preventing loss of neuronal cells and management of Alzheimer's disease.

Vitamin D3 administration prevents memory deficit and alteration of biochemical parameters induced by unpredictable chronic mild stress in rats.

The present study aimed to investigate the effects of vitamin D3 (Vit D) administration on memory function, hippocampal level of amyloid-beta (Aß), brain-derived neurotrophic factor (BDNF) and oxidative stress status in a rat model of unpredictable chronic mild stress (UCMS). Vit D was intraperitoneally administered at doses of 100, 1000, and 10,000 IU/kg. Animals were subjected to UCMS for a total period of 4 weeks. Memory function was assessed using morris water maze (MWM) and passive avoidance (PA) tests. Biochemical markers were measured to reveal the status of oxidative stress and antioxidant defense system. In addition, the levels of Aß and BDNF were measured in hippocampal region. In the UCMS group, latency to find the platform was greater and the time spent in target quadrant (MWM test) as well as the latency to enter the dark compartment (PA test), were less than the vehicle group. Hippocampal malondialdehyde (MDA) and Aß concentrations in the UCMS group were higher than the vehicle group. Hippocampal level of thiol and BDNF plus the activities of catalase and superoxide dismutase (SOD) were reduced in UCMS group compared to the control subjects (i.e. vehicle group). Interestingly, Vit D treatment supplementation reversed the mentioned effects of UCMS. Our findings indicated that Vit D administration improves UCMS-induced impairment of learning and memory through prevention of adverse effects on Aß, BDNF and oxidative stress parameters.

Increasing dietary choline attenuates spatial memory deficits resulting from exposure to the chemotherapeutic agents cyclophosphamide and doxorubicin.

BACKGROUND: Choline supplementation (+Ch) improves cognitive function in impaired animals and humans. Chemotherapy-related cognitive deficits (CRCDs) occur in cancer patients, and these deficits persist following treatment, adversely impacting quality of life. To date, there are no approved treatments for this condition. AIM: Because +Ch improves impaired memory, it was of interest to determine whether +Ch can attenuate spatial memory deficits induced by the chemotherapeutic agents doxorubicin (DOX) and cyclophosphamide (CYP). METHODS: Female BALB/C mice, 64 days of age, were trained in the Morris water maze and baseline performance determined on day 15. Following baseline assessment, mice were placed on +Ch diet (2.0% Ch) or remained on standard diet (0.12% Ch). Mice received intravenous injections of DOX (2.5 mg/kg) and CYP (25 mg/kg), or equivalent volumes of saline (0.9% NaCl), on days 16, 23, 30, and 37, and spatial memory was assessed weekly from day 22 to 71. RESULTS: DOX and CYP produced a prolonged impairment in spatial memory as indicated by an increased latency to the correct zone (p < 0.05), and a decrease in time in the correct zone (p < 0.05), % of total swim distance in the correct zone (p < 0.05) and % entries to the correct zone (p < 0.05). These effects were attenuated by +Ch. CONCLUSION: Although it remains to be determined whether this effect extends to other cognitive domains and whether +Ch is prophylactic or therapeutic, these findings suggest that +Ch may be an effective intervention for CRCDs.