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.

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.

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.

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.

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.

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.

Nattokinase prevents ß-amyloid peptide (Aß1-42) 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 ß-amyloid (Aß) 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 ß-Amyloid peptide (Aß1-42) induced neuropsychiatric conditions (depression-like behaviour, anxiety, and memory impairment) in mice. Aß1-42 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 Aß1-42 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.

Hippocampal delivery of neurotrophic factor-α1/carboxypeptidase E gene prevents neurodegeneration, amyloidosis, memory loss in Alzheimer's Disease male mice.

Alzheimer's Disease (AD) is a prevalent neurodegenerative disease characterized by tau hyperphosphorylation, Aß1-42 aggregation and cognitive dysfunction. Therapeutic agents directed at mitigating tau aggregation and clearing Aß1-42, and delivery of growth factor genes (BDNF, FGF2), have ameliorated cognitive deficits, but these approaches did not prevent or stop AD progression. Here we report that viral-(AAV) delivery of Neurotrophic Factor-α1/Carboxypeptidase E (NF-α1/CPE) gene in hippocampus at an early age prevented later development of cognitive deficits as assessed by Morris water maze and novel object recognition assays, neurodegeneration, and tau hyperphosphorylation in male 3xTg-AD mice. Additionally, amyloid precursor protein (APP) expression was reduced to near non-AD levels, and insoluble Aß1-42 was reduced significantly. Pro-survival proteins: mitochondrial Bcl2 and Serpina3g were increased; and mitophagy inhibitor Plin4 and pro-inflammatory protein Card14 were decreased in AAV-NF-α1/CPE treated versus untreated AD mice. Thus NF-α1/CPE gene therapy targets many regulatory components to prevent cognitive deficits in 3xTg-AD mice and has implications as a new therapy to prevent AD progression by promoting cell survival, inhibiting APP overexpression and tau hyperphosphorylation.

Endurance Exercise Training Attenuates the Waterpipe Smoke Inhaling-Induced Learning and Memory Impairment in Rats: Role of Neurotrophic Factors and Apoptotic System.

INTRODUCTION: The increasing prevalence of waterpipe tobacco smoking (WTS) and its detrimental effects on memory function have been reported. This study was conducted to investigate the effect of moderate-intensity endurance exercise on the detrimental effects of WTS on learning and spatial memory in rats. AIMS AND METHODS: Animals were divided into the Control group (CTL), the exercise group (Ex) which trained for 8 weeks, the WTS group (Wp) exposed to smoke inhalation (30 minutes per day, 5 days each week, and for 8 weeks), and the group that did exercise training and received waterpipe smoke together (Ex + Wp). Thereafter, learning and spatial memory were assessed by the Morris water maze test and hippocampal molecular measurements were done. RESULTS: Waterpipe smoke significantly impaired learning and spatial memory, decreased expression of neurotrophic factors IGF-1 and BDNF (p < .01 and p < .05 vs. CTL group, respectively), increased BAX to BCL-2 ratio (p < .001 vs. CTL group) in hippocampal tissue, and increased the percent of damaged neurons in the hippocampal CA1 area (p < .05 vs. CTL group). Combination of exercise training with WTS prevented learning and spatial memory disturbances and recovered expression of neurotrophic factors IGF-1 (p < .05 vs. Wp group), decreased BAX to BCL-2 ratio (p < .001 vs. Wp group), and reduced percentage of damaged neurons (p < .05 vs. Wp group). CONCLUSIONS: Findings suggest that moderate-intensity endurance exercise training can ameliorate learning and memory impairment caused by waterpipe smoke in rats. This effect partly results from increasing the expression of neurotrophic factors BDNF and IGF-1 and correcting pro/anti-apoptotic proteins balance in the hippocampal tissue. IMPLICATIONS: The popularity of WTS especially among youth is increasing. We assessed the effect of hookah smoke with/without exercise on learning and memory. Hookah smoke leads to CA1-neural injury and impairs learning and memory in rats. A combination of exercise training with hookah smoke attenuates these complications. This positive effect of exercise is partially mediated by the balancing of brain-derived neurotrophic factor (BDNF) and Insulin-like growth factor-1 (IGF-1) and also the BAX to BCL-2 ratio, a significant predictor of cell susceptibility to apoptosis. Extrapolation of these positive findings to humans needs complementary studies.

Moderate-intensity intermittent exercise prevents memory deficit, hippocampal neuron loss, and elevated level of Alzheimer's dementia markers in the hippocampus of trimethyltin-induced rats.

BACKGROUND: Moderate-intensity intermittent exercise (MIIE) has been proposed as an effective method for preventing Alzheimer's dementia (AD). AIM: This study aimed to investigate the effects of MIIE on the spatial memory and protein level of AD markers in the hippocampus of trimethyltin (TMT)-induced rat model of hippocampal degeneration. METHODS: Male Sprague Dawley (SD) rats were randomly assigned into four groups: normal control (N), exercise control (E), TMT control (T), and exercise and TMT (ET). Rats of the exercise groups (E and ET) were forced to run on a treadmill for 30 min each day at maximum for 12 weeks. Intraperitoneal injection of 8 mg/kgBW TMT was administered as a single dose, 10 days before the last exercise treatment for the T and ET groups. The spatial memory of rats was examined using Morris water maze (MWM) test after the exercise period. After euthanasia, the hippocampal tissue was dissected out and the level of hippocampal presenilin-1 (PSEN-1) and phosphorylated tau (p-tau) protein were measured using ELISA. The total number of hippocampal pyramidal neurons was estimated using unbiased stereological analysis. Qualitative immunohistochemistry was performed to examine the expression of brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) in paraffin sections of the hippocampus. RESULTS: TMT exposure induced memory impairment indicated by the T group having the lowest percentage of time and percentage of path length in the target quadrant compared to other groups. MIIE prevented the memory impairment effect of TMT exposure indicated by the ET group having no significantly different MWM performance compared to the E and N groups. The ET group had significantly lower levels of hippocampal AD markers, p-tau and PSEN-1, as well as significantly higher estimated total number of pyramidal neurons of hippocampal CA1 and CA2-3 regions compared to the T group. Expressions of TNF-α was weak, while the expression of IL-10 was stronger in the ET group compared to the control group. The TMT-induced group exhibited stronger expression of BDNF. CONCLUSION: MIIE prevents neuronal loss and impaired spatial memory upon TMT exposure most probably via preventing elevated levels of hippocampal AD markers and neuroinflammation. WC:350.

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.

Dexmedetomidine attenuates postoperative spatial memory impairment after surgery by reducing cytochrome C.

BACKGROUND: Anesthesia and surgery can induce perioperative neurocognitive disorders (PND). Mitochondrial dysfunction has been proposed to be one of the earliest triggering events in surgery-induced neuronal damage. Dexmedetomidine has been demonstrated to attenuate the impairment of cognition in aged rats induced by surgery in our previous study. METHODS: Male Sprague-Dawley rats underwent hepatic apex resection under anesthesia with propofol to clinically mimic human abdominal surgery. The rats were divided into three groups: Control group, Model group and Dexmedetomidine (Dex) group. Cognitive function was evaluated with the Morris water maze (MWM), Open Field Test (OFT)and Novel object recognition task (NOR). Ultrastructural change in neuronal mitochondria was measured by transmission electron microscopy. Mitochondrial function was measured by mitochondrial membrane potential and activities of mitochondrial complexes. Neuronal morphology was observed with H&E staining and the activation of glial cells was observed by immunohistochemistry in the hippocampus. Protein levels were measured by Western blot (WB) and immunofluorescence at 3 and 7 days after surgery. RESULTS: Surgery-induced cognitive decline lasts three days, but not seven days after surgery in the model group. Transmission electron microscope showed the mitochondrial structure damage in the model group, similar changes were not induced in the Dex group. Dexmedetomidine may reverse the decrease in mitochondrial membrane potential and mitochondrial complex activity. Compared with the Control group, the expression of cytochrome c was significantly increased in model group by Western blot and immunofluorescence on days 3, but not day 7. Rats from the Model group expressed significantly greater levels of Iba-1 and GFAP compared with the Control group and the Dex group. CONCLUSION: Dexmedetomidine appears to reverse surgery-induced behavior, mitigate the higher density of Iba-1 and GFAP, reduce the damage of mitochondrial structure and function by alleviating oxidative stress and protect mitochondrial respiratory chain, thus increasing cytochrome c oxidase (COX) expression and downregulate the expression of cytochrome c protein in the hippocampus of rats.

Taurine and N-acetylcysteine treatments prevent memory impairment and metabolite profile alterations in the hippocampus of high-fat diet-fed female mice.

Background: Obesity constitutes a risk factor for cognitive impairment. In rodent models, long-term exposure to obesogenic diets leads to hippocampal taurine accumulation. Since taurine has putative cyto-protective effects, hippocampal taurine accumulation in obese and diabetic models might constitute a counteracting response to metabolic stress. Objective: We tested the hypothesis that treatment with taurine or with N-acetylcysteine (NAC), which provides cysteine for the synthesis of taurine and glutathione, prevent high-fat diet (HFD)-associated hippocampal alterations and memory impairment. Methods: Female mice were fed either a regular diet or HFD. Some mice had access to 3%(w/v) taurine or 3%(w/v) NAC in the drinking water. After 2 months, magnetic resonance spectroscopy (MRS) was used to measure metabolite profiles. Memory was assessed in novel object and novel location recognition tests. Results: HFD feeding caused memory impairment in both tests, and reduced concentration of lactate, phosphocreatine-to-creatine ratio, and the neuronal marker N-acetylaspartate in the hippocampus. Taurine and NAC prevented HFD-induced memory impairment and N-acetylaspartate reduction. NAC, but not taurine, prevented the reduction of lactate and phosphocreatine-to-creatine ratio. MRS revealed NAC/taurine-induced increase of hippocampal glutamate and GABA levels. Conclusion: NAC and taurine can prevent memory impairment, while only NAC prevents alterations of metabolite concentrations in HFD-exposed female mice.

Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aß) plaques and neurofibrillary tangles. The best cellular correlates of the early cognitive deficits in AD patients are synapse loss and gliosis. In particular, it is unclear whether the activation of microglia (microgliosis) has a neuroprotective or pathological role early in AD. Here we report that microgliosis is an early mediator of synaptic dysfunction and cognitive impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We found that the appearance of microgliosis, synaptic dysfunction and behavioral impairment coincided with increased soluble Aß42 levels, and occurred well before the presence of Aß plaques. Inhibition of microglial activity by treatment with minocycline (MC) reduced gliosis, synaptic deficits and cognitive impairments at early pathological stages and was most effective when provided preventive, i.e., before the onset of microgliosis. Interestingly, soluble Aß levels or Aß plaques deposition were not affected by preventive MC treatment at an early pathological stage (4 months) whereas these were reduced upon treatment at a later stage (6 months). In conclusion, this study demonstrates the importance of early-stage prevention of microgliosis on the development of cognitive impairment in APP/PS1 mice, which might be clinically relevant in preventing memory loss and delaying AD pathogenesis.

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.

The Protective Effects of the Combination of Vitamin E and Swimming Exercise on Memory Impairment Induced by Exposure to Waterpipe Smoke.

BACKGROUND: Waterpipe smoking (WP) exposure involves a negative health impact, including memory deficit, which is attributed to the elevation of oxidative stress. Vitamin E (VitE) in combination with swimming exercise exerts protective effects that prevent memory impairment. In the current study, the modulation of WP-induced memory impairment by the combined effect of VitE and swimming exercise (SE) was investigated. METHODS: Animals were exposed to WP one hour/day, five days per week for four weeks. Simultaneously, VitE (100 mg/kg, six days/week for four weeks) was administered via oral gavage, and the rats were made to swim one hour/day, five days/week for four weeks. Changes in memory were evaluated using radial arm water maze (RAWM), and oxidative stress biomarkers were examined in the hippocampus. RESULTS: WP exposure induced short-term/long-term memory impairment (p<0.05). This impairment was prevented by a combination of VitE with SE (p<0.05). Additionally, this combination normalized the hippocampal catalase, GPx, and GSH/GSSG ratios that were modulated by WP (p<0.05). The combination further reduced TBARs levels below those of the control group (p<0.05). CONCLUSION: WP-induced memory impairments were prevented by the combination of VitE with SE. This could be attributed to preserving the hippocampal oxidative mechanism by combining VitE and SE during WP exposure.

Neuropharmacological effects of honey in lipopolysaccharide-induced neuroinflammation, cognitive impairment, anxiety and motor impairment.

Objectives: Honey contains phenolic acids and flavonoids, which are significant in developing drugs against neuroinflammation. The study was designed to evaluate the ameliorative potential of honey in lipopolysaccharides-induced neuroinflammation.Methods: Thirty male Wistar rats were divided into six groups, namely: the control group (10 mL/kg vehicle), the LPS only group (250 µg/kg), the honey (0.26, 0.31 and 0.36 g/kg) and the ibuprofen (100 mg/kg). LPS (250 µg/kg i.p) was administered for 7days followed by the treatment with honey and Ibuprofen for another 7days. Animals were assessed for memory impairment and anxiety levels using a Novel object recognition test (NORT), elevated plus maze (EPM), and open field test (OFT). Brain levels of pro-inflammatory cytokine level, acetylcholinesterase activity, and oxidative stress were determined. The neuronal alteration was assessed histologically using cresyl fast violet staining of the hippocampus, prefrontal cortex, and striatum.Results: Honey (0.31 and 0.36 g/kg) significantly ameliorated LPS-induced memory impairment on NORT and increased time spent in the open arm and increased the locomotor activity in the OFT. Honey significantly (p < 0.05) reduced LPS-induced elevation of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). It significantly reduced malondialdehyde and nitrite levels in mice brains and reversed depletion of reduced glutathione levels. Honey attenuated LPS-induced elevation of acetylcholinesterase activity in rat brains. Cresyl violet staining showed the restoration of neuronal organization and Nissl body distribution in the hippocampus, prefrontal cortex and striatum compared to the LPS only group.Discussion: Honey effectively ameliorated LPS-induced poor cognitive performance, anxiety, motor coordination responses to neuroinflammation, and oxidative stress.

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.