Reference Memory Errors Research Articles

The Effect of a Mediterranean and Western Diet on Cognitive Performance in Middle‐Aged Rats

AbstractBackgroundClinical studies indicate that mid‐life dietary patterns are a risk factor for cognitive decline. Adherence to a Mediterranean diet (MeDi) may promote healthy brain aging in contrast to a Western diet (WD), yet these diets have not been examined in pre‐clinical models. We hypothesized that consumption of the MeDi would have better cognitive performance compared to the Western diet in middle‐aged rats.MethodA subset of animals that provided diet‐specific fecal samples were used in this pilot study. Four‐month‐old male Fischer 344 rats were randomly assigned to a MeDi (n = 13) or WD (n = 7) for approximately one year. Animals then underwent neurobehavioral assessments including the Y‐maze, Morris water maze, and water radial arm maze to assess aspects of short‐ and long‐term memory. Data were analyzed via Student’s T‐test or Two‐Way Repeated Measures ANOVA where appropriate.ResultFor the Y‐maze, there was no difference in percent correct alternations between diet groups (p = 0.24), but the MeDi group had more total alternations compared to the WD group (p = 0.04). For the Morris Water Maze, the MeDi group had a decreased latency compared to the WD group (p = 0.03). Additionally, there was a Day x Diet Effect where the MeDi group had a decreased latency on days 3‐5 (p ≤ 0.01) compared to the WD group. There was no difference between diet groups for platform probe testing (p = 0.80). For the water radial arm maze, there was no difference in total (p = 0.56), working memory correct (p = 0.73), or working memory incorrect (p = 0.33) errors between diet groups. However, the WD group committed more reference memory errors compared to the MeDi group (p = 0.01).ConclusionMiddle‐aged animals consuming a MeDi demonstrated better aspects of learning and memory compared to animals consuming a WD. This data helps support clinical data suggesting that mid‐life dietary patterns impact cognitive function.

The Combined Effect of Tribulus terrestris Hydroalcoholic Extract and Swimming Exercise on Memory and Oxidative Stress in Old Male Rats

ABSTRACT Background and objective This study aims to assess the effect of swim exercise along with consumption of bindii hydroalcoholic extract on memory and the oxidative stress markers in old male rats. Materials and methods This study was conducted on 32 old (400–500 g) and eight young male Wistar rats. The groups included young, old, old bindii (200 mg/kg), old exercise, and old bindii exercise (concurrent swimming training). All interventions were performed within 14 days. The animals’ spatial memory was evaluated by the Y maze, radial maze, and shuttle box, Oxidative stress factors were also measured. Results Compared to the old control group, the bindii extract along with swimming exercise significantly increased the periodic behavior percentage in the Y maze and the delay time in entry into the dark chamber in the shuttle box but no significant difference was seen in the reference memory error in the radial maze. Also, a significant increase in the amount of catalase (CAT) and antioxidant capacity (TAC) and a significant decrease in the amount of malondialdehyde (MDA) were observed in all treatment groups. Conclusion These results show that exercise, along with the bindii extract consumption, can improve spatial and avoidance memory in old rats probably through the reduction of oxidative stress effects.

Effects of agmatine on radial-arm maze memory performance and autistic-like behaviors in a male rat model of autism.

Autism spectrum disorder (ASD) is the fastest-growing child neuropsychiatric condition. Cognitive dysfunctions such as memory impairments are experienced by patients along with social disturbances and repetitive/stereotypic movements. We have used the radial arm maze (RAM), for measurement of working and reference memory errors in an animal model of autism. In addition, the potential effects of agmatine, an endogenous NMDA antagonist, on RAM performance and autistic-like behaviors were assessed. Autism was modeled by valproic acid (VPA) administration at gestational Day 12.5. Autism-associated behaviors in male offspring were examined in an open field test (OFT) and three-chambered test (TCT) on postnatal days 50-51. Thereafter, the animals were trained in the RAM (PND 55) until they attained the criteria of 80% correct choices during five consecutive trials. Forty-eight hours after the acquisition of criteria, agmatine was injected 30 min before subsequent behavioral testing, which included the retention phase of the RAM, OFT, and TCT. VPA-treated and intact rats showed the same performance in RAM, and acute injection of agmatine rescued social and anxiety-like behavior induced by VPA without the effect on RAM. In a rat model of autism, spatial learning, and memory did not change. Agmatine rescued social and anxiety-like behavior in autistic animals.

Memory protective effect of Phyllanthus emblica against scopolamine induced spatial memory loss in male Long Evan Rats tested by Radial Arm Maze

Background: Dementia is the commonest problem of middle aged and elderly subjects due to age related changes and oxidative stress. Many traditional herbal agents including Emblica Officinalis (Phyllantus Emblica) demonstrated its benefit against memory loss. Objective: To investigate the protective effect of Ethanolic extract of Phyllantus Emblica (EEPE) or Emblica Officinalis in scopolamine induced memory impaired male Long Evan rats. Methods: This animal behavioral study was carried out on total 18 male long Evan rats weighing 300-400gm. According to treatment they were divided into NS (control) group (n=6, normal saline 5ml/kg) Sco(n=6; Scopolamine 2mg/kg) and PE(n=6; EEPE 400mg/kg+ Scopolamine 2mg/kg).This experiment was conducted for total 33 days. After 7 days acclimatization NS group and PE rats were treated with normal saline and EEPE respectively for consecutive 26 days. Scopolamine was given to sco group and PE group from day 22 to 26 (5 days during acquisition phase. Spatial memory (working and reference memory error) was assessed by 8 arm radial arm maze (RAM). Statistical analysis was done by ANOVA followed by Bonferroni’s post hoc test. Result: Working memory error (WME) as well as reference memory error (RME) was found significantly higher in scopolamine treated rats compared to normal memory as well as PE pretreated rats whereas no significant difference was found in WME and RME between normal memory rats and PE pre- treated rats. Conclusion: Phyllanthus Emblica can prevent memory impairment in scopolamine induced memory loss in Long Evan rats. J Bangladesh Soc Physiol 2022;17(2): 101-110

Mind the ramp: Association between early life ramp use and spatial cognition in laying hen pullets.

Ramps facilitate earlier access to complex environments and increase early life voluntary exercise, which may positively affect the cognitive development of chickens. This study focused on quantifying individual differences in ramp use and its impact on spatial cognition of laying hen pullets. Sixteen identical pens were housed with Lohmann Selected Leghorn (LSL) chicks of which eight chicks from each pen were colour marked from one day of age (DoA) to serve as focal birds. We quantified overall ramp use (walk/run, wing-assisted incline running, and jump/fly to and from ramps) by scan sampling recorded videos for 6, 10, 12, 20, 27, 41, and 55 DoA for all focal birds. From 56 to 95 DoA, long and short-term spatial memory of three focal birds per pen were assessed in a holeboard test in three consecutive phases: cued, uncued and reversal. Mixed model analysis showed that the spatial cognitive abilities of the birds were linked to differences in ramp use frequency averaged across all observation days. Birds with higher ramp use made fewer reference (Estimate ± Confidence Interval = 0.94 [0.88, 0.99], p = 0.08) and working memory errors (Est ± CI = 0.77 [0.59, 1.00], p = 0.06) in the cued phase than birds with lower ramp use. In contrast, birds with higher ramp use made more reference memory errors (Est ± CI = 1.10 [1.01, 1.20], p = 0.05) in the reversal phase. Birds with higher ramp use also made more reference memory errors compared to birds with lower ramp use as the phases changed from cued to uncued (p = 0.001). Our results indicate that there might be a relationship between early life ramp use and spatial cognition of laying hens.

Digestive and Absorptive Properties of the Antarctic Krill Tripeptide Phe-Pro-Phe (FPF) and Its Auxiliary Memory-Enhancing Effect.

Aging and stress have contributed to the development of memory disorders. Phe-Pro-Phe (FPF) was identified with high stability by mass spectrometry from simulated gastrointestinal digestion and everted gut sac products of the Antarctic krill peptide Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR) which was found to have a positive impact on memory enhancement. This study investigated the digestive stability, absorption, and memory-enhancing effects of FPF using nuclear magnetic resonance spectroscopy, simulated gastrointestinal digestion, in vivo fluorescence distribution analysis, mouse behavioral experiments, acetylcholine function, Nissl staining, immunofluorescence, and immunohistochemistry. FPF crossed the blood-brain barrier into the brain after digestion, significantly reduced shock time, working memory errors, and reference memory errors, and increased the recognition index. Additionally, FPF elevated ACh content; Nissl body counts; and CREB, SYN, and PSD-95 expression levels, while reducing AChE activity (P < 0.05). This implies that FPF prevents scopolamine-induced memory impairment and provides a basis for future research on memory disorders.

Effect of thymol on oxidative stress and reelin signaling pathway in Alzheimer's disease model.

The purpose of this study was to investigate how thymol affects cognitive functions and the levels of MDA, GSH, Aβ1-42, ApoE, reelin, and LRP8 in an AD model induced in male Wistar albino rats with the application of D-galactose (D-gal) and aluminum chloride (AlCl3). In this work, 3-month-old male Wistar albino rats were used. Group 1 served as the Control, Group 2 received 0.5 mL/day saline + 0.5 mL/day sunflower oil, Group 3 was administered 200 mg/kg/day AlCl3 + 60 mg/kg/day D-gal, Group 4 received 30 mg/kg/day thymol, and Group 5 was administered 200 mg/kg/day AlCl3 + 60 mg/kg/day D-gal + 30 mg/kg/day thymol. At the end of the 10-week experimental period, behavioral and memory tests were performed. GSH and MDA levels were measured in the obtained serum and brain tissue samples, while Aβ1-42, ApoE, reelin, and LRP8 levels were measured in brain tissue samples. Statistical analyses were performed using ANOVA test in Graphpad Prism V8.3 program. A p-value <0.05 was considered significant in intergroup analyses. When the novel object recognition test (NORT) results were evaluated, the Alzheimer + thymol (ALZ+TYM) group showed a significant increase in the recognition index (RI) and discrimination index (DI) compared to the Alzheimer (ALZ) group at the 24th hour. Thymol reduced working memory errors (WME), reference memory errors (RME), and maze completion time at 48, 72, and 96 hours when evaluated in terms of spatial memory in rats with Alzheimer's disease. Furthermore, Aβ1-42 and ApoE levels were increased in the ALZ group compared to the control (C), while reelin and LRP8 levels were decreased in the ALZ group compared to the C group. The data we obtained suggest that thymol may play an effective role in cognitive processes against AD and have an anti-Alzheimer's disease effect.

The Edible Seaweed Gelidium amansii Promotes Structural Plasticity of Hippocampal Neurons and Improves Scopolamine-Induced Learning and Memory Impairment in Mice.

Gelidium amansii has been gaining profound interest in East Asian countries due to its enormous commercial value for agar production and its extensive pharmacological properties. Previous studies have shown that the ethanol extract of Gelidium amansii (GAE) has promising neurotrophic effects in in vitro conditions. The present study aimed at investigating the protective effects of GAE against scopolamine-induced cognitive deficits and its modulatory effects on hippocampal plasticity in mice. For memory-related behavioral studies, the passive avoidance test and radial arm maze paradigm were conducted. The brain slices of the hippocampus CA1 neurons of experimental mice were then prepared to perform Golgi staining for analyzing spine density and its characteristic shape, and immunohistochemistry for assessing the expression of different pre- and postsynaptic proteins. Following oral administration of GAE (0.5 mg/g body weight), mice with memory deficits exhibited a significant increase in the latency time on the passive avoidance test and a decrease in the number of working and reference memory errors and latency time on the radial arm maze test. Microscopic observations of Golgi-impregnated tissue sections and immunohistochemistry of hippocampal slices showed that neurons from GAE-treated mice displayed higher spine density and spine dynamics, increased synaptic contact, and the recruitment of memory-associated proteins such as N-methyl-D-aspartate receptors (NR2A and NR2B) and postsynaptic density-95 (PSD-95) when compared with the control group. With these memory-protective functions and a modulatory role in underlying memory-related events, GAE could be a potential functional food and a promising source of pharmacological agents for the prevention and treatment of memory-related brain disorders.

Fecal microbiota transplantation and short-chain fatty acids improve learning and memory in fluorosis mice by BDNF-PI3K/AKT pathway

Fluoride, an environmental toxicant, not only arouses intestinal microbiota dysbiosis, but also causes neuronal apoptosis and a decline in learning and memory ability. The purpose of this study was to explore whether fecal microbiota transplantation (FMT) from healthy mice and bacteria-derived metabolites short-chain fatty acids (SCFAs) supplement protect against fluoride-induced learning and memory impairment. Results showed that FMT reversed the elevated percentage of working memory errors (WME) and reference memory errors (RME) in fluorosis mice during the eight-arm maze test. Nissl and TUNEL staining presented that fluoride led to a decreased proportion of Nissl bodies area in the hippocampal CA3 region and an increased apoptotic ratio of nerve cells in CA1, CA3 and DG areas, whereas FMT alleviated those pathological damages. Moreover, the expressions of mRNA in hippocampal BDNF, PDK1, AKT, Bcl-2, and Bcl-xL were downregulated in mice exposed to fluoride, but the levels of PI3K, Bax, Bak, and Caspase-7 mRNA were upregulated. NaF treatment had an increase in PI3K and Caspase-3 protein levels and reduced the expressions of these four proteins, including BDNF, p-PI3K, AKT and p-AKT. By contrast, FMT enhanced the expression of BDNF and thus activated the PI3K/AKT pathway. Besides, the 16S rRNA sequencing revealed that fluoride caused a reduction in certain SCFA producers in the colon as evidenced by a decline in Erysipelatoclostridiaceae, and a downward trend in Akkermansia, Blautia and Alistipes. However, the disordered gut microbiome was restored via frequent FMT. Of note, SCFAs administration also increased BDNF levels and regulated its downstream pathways, which contributed to cell survival and learning and memory function recovery. In conclusion, FMT and SCFAs may activate the BDNF-PI3K/AKT pathway to play an anti-apoptotic role and ultimately improve learning and memory deficits in fluorosis mice.

Mechanism of Bugansan Decoction in ameliorating learning and memory impairment in D-galactose-induced aging rats based on AGEs/RAGE/NF-κB pathway

ObjectiveTo investigate the underlying mechanism of the compound Bugansan Decoction (补肝散, BGSD) in intervening learning and memory in D-galactose (D-gal)-induced aging rats. MethodsA total of 40 rats were randomly assigned to four groups: control, model, BGSD [14.06 g/(kg·d)], and piracetam [0.4 g/(kg·d)] groups, with 10 rats in each group. D-gal [400 mg/(kg·d)] was injected intraperitoneally to establish the aging rat model. The rats' body weight, water intake, food intake, and gripping strength were recorded each week. The eight-arm maze and step-down test were used to measure the rats' capacity for learning and memory. Liver, thymus, spleen, and brain tissues were weighed to calculate the corresponding organ indices; serum malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured. Hematoxylin and eosin (HE) staining was adopted to observe the pathological changes of the hippocampus; enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the hippocampus. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of receptors for advanced glycation end products (RAGE), nuclear factor-κB (NF-κB), TNF-α, IL-6, and IL-1β mRNA in the hippocampus. Western blot (WB) was employed to detect the expression levels of advanced glycation end products (AGEs), RAGE, and NF-κB protein in the hippocampus. ResultsIn D-gal-induced aging rats, BGSD significantly increased food intake, water intake, body weight, gripping strength, and organ indices (P < 0.05), and significantly decreased working memory error (WME), reference memory error (RME), and total memory errors (TE) in an eight-arm maze (P < 0.05). In the step-down test, step-down latency was prolonged and the frequency of errors dropped (P < 0.05). Additionally, BGSD could lessen the harm done to hippocampus neurons, increase serum SOD activity, lower MDA levels, and down-regulate the expression levels of the pro-inflammatory molecules TNF-α, IL-6, and IL-1β (P < 0.05). Further findings showed that BGSD significantly decreased hippocampal AGEs, RAGE, and NF-κB expression (P < 0.05). ConclusionBy blocking the AGEs/RAGE/NF-κB signaling pathway, BGSD may regulate the neuroinflammatory damage in D-gal-induced aging rats, and thus improve learning and memory.

Effects of long-term individual housing of middle-aged female Octodon degus on spatial learning and memory in the Barnes maze task.

Prolonged social isolation is a form of passive chronic stress that has consequences on human and animal behavior. The present study was undertaken to elucidate whether the long-term isolation would precipitate age-related changes in anxiety and spatial learning and memory in degus. We investigated the effects of long-term social isolation on anxiety levels in the light-dark test, and spatial orientation abilities in the Barnes maze. Middle-aged female Octodon degus were allocated to either group-housed (3 animals per cage) or individually-housed for 5 months. Under this experimental condition, there were no significant group differences in the anxiety level tested in the light-dark test and in the motivation to escape from the Barnes maze. There were no significant differences in cortisol levels between individually- and group-housed animals. On the last acquisition training day of spatial learning, individually- housed animals had a significantly higher number of correct responses and a smaller number of reference and working memory errors than the group-housed animals. In addition, isolated animals showed a tendency for reference and working memory impairment on the retention trial, while group-housed degus showed improvement in these parameters. The present study indicates that prolonged social isolation during adulthood in female degus has a dual effect on spatial orientation. Specifically, it results in a significant improvement in acquisition skills but a slight impairment in memory retention. The obtained cognitive changes were not accompanied by modification in anxiety and cortisol levels.

Exploring potential strategies to enhance memory and cognition in aging mice

Background: Aging population is rapidly expanding worldwide, and age-related cognitive impairments prove detrimental for achieving a better productive and quality of life. Lack of effective therapies for age-related cognitive impairment focuses attention on developing preventive strategies, such as nutritional interventions, cell therapies and environmental manipulations. The objective of the present study was to explore the comparative benefits of potential memory-enhancing strategies like supplementation of choline (Ch) and docosahexaenoic acid (DHA) or administration of human embryonic kidney stem cell conditioned media (HEK-CM) or exposure to environmental enrichment (EE), that attenuates cognitive impairments in aging mice. Methods: 12-month-old CF1 male mice were subdivided [n=6/group] into normal aging control (NAC), saline vehicle control (SVC), Ch-DHA, EE, heat-inactivated HEK-CM (HIHEK-CM) and HEK-CM mice. Spatial working and reference memory were assessed using an eight-arm radial maze test and cognition using a novel object recognition test (NORT). Results: Spatial memory and cognition were decreased in normal aging mice. Aged mice exposed to dietary Ch-DHA or HEK-CM showed significant enhancement in spatial learning tasks, memory and cognition compared to the same in age-matched NAC mice. Ch-DHA and HEK-CM treated mice committed significantly lesser reference memory errors and attained a higher percentage of correct choices in spatial learning and memory tasks. Moreover, on testing for cognition in NORT, significantly higher number of visits to the novel object was observed in Ch-DHA supplemented and HEK-CM administered aging mice whereas HEK-CM and EE mice groups showed significantly greater number of visits to familiar object, when compared to same in age-matched NAC and HIHEK-CM groups, respectively. Conclusion: Supplementation of Ch-DHA and HEK-CM treatment strategies have a higher potential [~ 20—30%] for enhancing spatial learning, memory and cognition in normal aged mice, whereas exposure to EE seems to enhance only their short-term memory.

Nattokinase prevents β-amyloid peptide (Aβ1-42) induced neuropsychiatric complications, neuroinflammation and BDNF signalling disruption in mice

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized by abnormal accumulation of extracellular β-amyloid (Aβ) plaques and neuronal damage. Although AD is typically considered a cognitive neurodegenerative disorder, almost all people diagnosed with AD develop neuropsychiatric complications at some stage in their life span. The present study investigated the effect of chronic Nattokinase (NK) administration on β-Amyloid peptide (Aβ1-42) induced neuropsychiatric conditions (depression-like behaviour, anxiety, and memory impairment) in mice. Aβ1-42 peptide injected mice demonstrated depression, anxiety, and impairment of cognitive abilities evaluated as increased immobility time in forced swim test (FST), decreased open arm time/entries in elevated plus maze (EPM) and reference and working memory error in radial arm maze (RAM) respectively with elevation in Interleukin-6 (IL-6), Tumour necrosis factor-α (TNF-α), reduction in Interleukin-10 (IL-10) and Brain-derived neurotrophic factor (BDNF) immunocontent within the hippocampus. Chronic administration of NK (50–100 mg/kg, i.p.) from day 8–27, prevented depression-like behaviour, anxiety, and memory impairment and normalized the neurochemical alteration within the hippocampus of mice injected with Aβ1-42 peptide. The effect of NK on psychiatric complications, learning, and memory was comparable to peripheral donepezil treatment. This study suggests that NK improves learning, memory impairment, and neuropsychiatric complications possibly through the downregulation of neuroinflammatory pathways and restoring BDNF signalling in AD.

Rosmarinus officinalis and Mentha piperita Oils Supplementation Enhances Memory in a Rat Model of Scopolamine-Induced Alzheimer's Disease-like Condition.

Alzheimer's disease is regarded as a common neurodegenerative disease that may lead to dementia and the loss of memory. We report here the nootropic and anti-amnesic effects of both peppermint and rosemary oils using a rat model of scopolamine-induced amnesia-like AD. Rats were administered orally with two doses (50 and 100 mg/kg) of each single oil and combined oils. The positive group used donepezil (1 mg/kg). In the therapeutic phase, rats were administered scopolamine (1 mg/kg) through the oral administration of oils. During the nootropic phase, both oils showed a significant (p < 0.05) decrease in radial arm maze latency times, working memory, and reference memory errors compared with the normal group, along with significant (p < 0.05) enhancements of long-term memory during the passive avoidance test. Therapeutic phase results revealed significant enhancements of memory processing compared with the positive groups. In the hippocampus, oils exhibited an elevation of BDNF levels in a dose-dependent manner. Immunohistochemistry findings showed increased hippocampal neurogenesis suppressed by scopolamine in the sub-granular zone, and the anti-amnesic activity of single oil was enhanced when the two oils combined. Gas chromatography-mass spectrometry (GCMS) of the two oils revealed sufficient compounds (1,8-Cineole, α-Pinene, menthol and menthone) with potential efficacy in the memory process and cognitive defects. Our work suggests that both oils could enhance the performance of working and spatial memory, and when combined, more anti-amnesic activity was produced. A potential enhancement of hippocampal growth and neural plasticity was apparent with possible therapeutic activity to boost memory in AD patients.

Landmark-dependent Navigation Strategy Declines across the Human Life-Span: Evidence from Over 37,000 Participants

Humans show a remarkable capacity to navigate various environments using different navigation strategies, and we know that strategy changes across the life span. However, this observation has been based on studies of small sample sizes. To this end, we used a mobile app-based video game (Sea Hero Quest) to test virtual navigation strategies and memory performance within a distinct radial arm maze level in over 37,000 participants. Players were presented with six pathways (three open and three closed) and were required to navigate to the three open pathways to collect a target. Next, all six pathways were made available and the player was required to visit the pathways that were previously unavailable. Both reference memory and working memory errors were calculated. Crucially, at the end of the level, the player was asked a multiple-choice question about how they found the targets (i.e., a counting-dependent strategy vs. a landmark-dependent strategy). As predicted from previous laboratory studies, we found the use of landmarks declined linearly with age. Those using landmark-based strategies also performed better on reference memory than those using a counting-based strategy. These results extend previous observations in the laboratory showing a decreased use of landmark-dependent strategies with age.

Memory-Enhancing and Antioxidant Activities of the Hydroethanolic Leave Extract of Piliostigma reticulatum (Fabaceae) in the Monosodium Glutamate-Induced Alzheimer's Disease Model

Background: Piliostigma reticulatum (Fabaceae) is a plant used in Cameroon for the treatment of madness and migraine. Aims and Objectives: This study aims to evaluate the memory-enhancing and antioxidant activities of the hydroethanolic leaves extract of PR in the monosodium glutamate-induced Alzheimer's disease model. Materials and Methods: The Y-maze, Radial-arm maze and Novel object recognition tests were used to assess short, and long-term memory. At the end of the experiments, the brains of mice were scavenged for biochemical and histological analysis. Results: It was observed that the hydroalcoholic extract of PR leaf significantly reversed the percentage of spontaneous alternation compared to the negative control group at the different doses tested (p&lt;0.01; p&lt;0.001) in the Y-maze test. In the radial arm maze test, the extract significantly (p&lt;0.001) reduced the time spent consuming the bait, the number of reference memory and working memory errors at all doses. The treatment of animals with hydroethanolic extract of PR resulted in a significant increase in the discrimination index (p&lt;0.001) in the unfamiliar object recognition test. In addition, the extract significantly (p &lt; 0.01); p &lt; 0.001) decreased acetylcholinesterase activity,and MDA levels at all tested doses; and significantly (p &lt; 0.05; p &lt; 0.001) increased SOD level and Catalase activity in comparison to the negative control group. The histological analysis showed that the extract of Piliostigma reticulatum protected the different structures of the hippocampus against damage caused by monosodium glutamate. Conclusion : The memoryenhancing induced by the hydroethanolic leaves extract of Piliostigma reticulatum could be due to his antioxidant and anticholinesterase properties. These effects could justify the use of this plant to manage nervous system affections.

Exploring potential strategies to enhance memory and cognition in aging mice

Background: Aging population is rapidly expanding worldwide, and age-related cognitive impairments prove detrimental for achieving a better productive and quality of life. Lack of effective therapies for age-related cognitive impairment focuses attention on developing preventive strategies, such as nutritional interventions, cell therapies and environmental manipulations. The objective of the present study was to explore the comparative benefits of potential memory-enhancing strategies like supplementation of choline (Ch) and docosahexaenoic acid (DHA) or administration of human embryonic kidney stem cell conditioned media (HEK-CM) or exposure to environmental enrichment (EE), that attenuates cognitive impairments in aging mice. Methods: 12-month-old CF1 male mice were subdivided [n=6/group] into normal aging control (NAC), saline vehicle control (SVC), Ch-DHA, EE, heat-inactivated HEK-CM (HIHEK-CM) and HEK-CM mice. Spatial working and reference memory were assessed using an eight-arm radial maze test and cognition using a novel object recognition test (NORT). Results: Spatial memory and cognition were decreased in normal aging mice. Aged mice exposed to dietary Ch-DHA or HEK-CM showed significant enhancement in spatial learning tasks, memory and cognition compared to the same in age-matched NAC mice. Ch-DHA and HEK-CM treated mice committed significantly lesser reference memory errors and attained a higher percentage of correct choices in spatial learning and memory tasks. Moreover, on testing for cognition in NORT, significantly higher number of visits to the novel object was observed in Ch-DHA supplemented and HEK-CM administered aging mice whereas HEK-CM and EE mice groups showed significantly greater number of visits to familiar object, when compared to same in age-matched NAC and HIHEK-CM groups, respectively. Conclusion: Supplementation of Ch-DHA and HEK-CM treatment strategies have a higher potential [~ 20—30%] for enhancing spatial learning, memory and cognition in normal aged mice, whereas exposure to EE seems to enhance only their short-term memory.

Metformin mitigates amyloid β1-40-induced cognitive decline via attenuation of oxidative/nitrosative stress and neuroinflammation.

Metformin is an antidiabetic medicine widely used for management of type 2 diabetes with neuroprotective effects and promising potential to attenuate cognitive impairment. The efficacy of metformin in attenuation of Alzheimer's disease (AD) pathology has not been well-documented. Thus, this study was designed to assess protective effect of metformin against Aβ1-40-instigared cognitive impairment. After intra-CA1 microinjection of aggregated Aβ1-40, rats received oral metformin (50 and/or 200mg/kg/day) for two weeks. Cognition function was analyzed in various behavioral tasks besides measurement of hippocampal oxidative stress, apoptosis, and inflammation along with H&E staining and 3-nitrotyrosine (3-NT) immunohistochemistry. Obtained data showed significant improvement of discrimination score in novel object recognition test, higher alternation score in Y maze, greater latency in passive avoidance task, and lower working and reference memory errors in radial arm maze in metformin-treated Aβ-injured group. Moreover, metformin treatment attenuated hippocampal levels of nitrite, MDA, protein carbonyl, ROS, TNFα, GFAP, DNA fragmentation intensity, caspase 3 activity, AChE activity, and increased SOD activity and level of IL-10 as an anti-inflammatory factor. In addition, metformin treatment was associated with lower CA1 neuronal loss and it also decreased intensity of 3-NT immunoreactivity as an indicator of nitrosative stress. Taken together, obtained findings showed neuroprotective and anti-dementia property of metformin in male rats and this may have potential benefit in attenuation of cognitive decline and related complications in patients with neurodegenerative disorders such as AD besides diabetes mellitus.

Oral bioavailability and neuroprotective effect of a novel food-grade formulation of fisetin using fenugreek-galactomannan hydrogel scaffolds

BackgroundDespite the beneficial pharmacological effects, poor oral bioavailability limits the nutritional efficacy of fisetin, a dietary flavonoid. To this end, herein we report the bioavailability and efficacy of an innovative formulation of fisetin using a fenugreek-galactomannan hydrogel scaffold (FF-20). MethodsIn the first phase of the study, female Wistar rats (n = 42) were randomly divided into two groups (n = 21/group) and orally administered with either unformulated (UF) or FF-20 (50 mg/kg b. wt.) and plasma concentration of fisetin was estimated by UPLC-ESI-MS/MS. In the second phase, the relative influence of FF-20 on alcohol-induced neurotoxicity was followed on animals (n = 24) randomized into four groups, Group I – vehicle control, Group II – ethanol treated, Group III – ethanol+ UF, and Group IV – ethanol + FF-20 and treated at 50 mg/kg b. wt. per day for 14 days. ResultsArea under plasma concentration verses time curve showed 9.83-fold enhancement in bioavailability for FF-20, with significantly enhanced pharmacokinetic parameters (*** P < 0.001). Behavior studies revealed significant improvement in reference memory errors, working memory errors, and anxiety among fisetin-treated animals and the improvement was significant in FF-20, compared to UF (* P < 0.05). Neurotransmitters and gene expressions of NMDAR, MAO A&B, and KLF-11 were altered by alcohol treatment; but were restored/improved in FF-20 group. Histopathology of brain tissues also indicated the reversal of alcohol-induced necrosis and tissue damage by FF-20. ConclusionFF-20 enhanced the oral bioavailability and significantly alleviated alcohol-induced neurotoxicity in experimental rats.

Evaluation of Antiamnesic and Cholinesterase inhibitory effects of Illicium verum hook.f (Star anise) against Scopolamine induced memory impairment in Mice

Objectives: The current study is carried out on the methanol extract of Illicium verum hook.f (MEIV) to evaluate and examine anti-amnesic effects of Illicium verum hook.f by using the radial arm maze model. Study design and setting: This experimental observational study was performed in the Department of Pharmacology, Hamdard university from 20th November 2017 to 20th May 2018. after ethical approval from Board of Advanced studies and Research. Methodology: Total N=30 healthy albino mice were treated with graded doses of methanol extract of Illicium verum hook.f (MEIV) (300 and 500mg/kg p.o.) to verify its effectiveness regarding scopolamine induce memory impairment. Afterward, in-vitro studies were performed on isolated parts of brain mice by using an F2000 fluorescent spectrophotometer (Hitachi) to analyze the acetylcholinesterase level. Results: Investigation reveals that methanol extracts of Illicium verum hook.f (MEIV) by oral administration reduces the incidence of working and reference memory errors additionally this investigation was proved that active avoidance responses in scopolamine-treated group decreased. The acetylcholine esterase level was significantly reduced at the dose of 300 mg/kg (102.05±1.93µmol/min/mg) as compared to the positive control group (161.33±2.347 µmol/min/mg). Conclusion: Based on behavioral and biochemical investigations, we concluded that MEIV produces anti-amnesic effects by the inhibition of acetylcholinesterase, which might be due to the presence of various essential phytochemicals such as alkaloids, flavonoids, triterpenoid, polyphenols. Our finding reveals that Illicium verum is among the screened plants to be assessed further as an herbal substitute for the treatment of Alzheimer's disease