Injection Of Scopolamine Research Articles

P1‐207: NEUROPROTECTIVE EFFECT OF POLYPHENOLIC RICH EXTRACT OF AEGLE MARMELOS IN ALZHEIMER'S DISEASE LIKE PATHOLOGY VIA MAINTAINING OXIDATIVE BALANCE AND ACETYLCHOLINE LEVEL

Alzheimer's disease (AD) is a progressive neurodegenerative mental disorder amongst aging people which is associated with impairment in cognitive functions. Free radicals as well as cholinergic deficit neuron within nucleus basalis magnocellularis further attributed with aggregation of β amyloid contributes as an essential hallmark in AD. Hydroethanolic extract of Aegle marmelos (HEAM) fruit pulp was quantitatively estimated for individual polyphenolic compounds by HPLC-DAD analysis which exhibited the presence of rich amount of chlorogenic acid, protocatechuic acid and caffeic acid. In present study we estimated the neuropharmacological potential of HEAM on hippocampal memory deficit induced by scopolamine injection in rodents. Swiss albino mice were orally preadministered with HEAM (200, 400, and 600 mg/kg) and Donepezil (1mg/kg) for 21days. To assess cognitive function, Elevated plus maze and Hebbs William maze task were performed for consecutively 2 days. Homogenized brain hippocampus was used for enzymatic antioxidant level, AChE inhibitory activity determination as well as gene expression determination. Scopolamine injection elevated the TL (transfer latency) and TRC (Time taken to reach the reward chamber), which were significantly reversed by pretreatment with HEAM in a dose dependent manner. In addition, acetylcholinesterase activity, enzymatic and nonenzymatic oxidant-antioxidant balance level, neurogenesis and their concerning pathways were markedly distorted by scopolamine in hippocampal region, whereas those impairments were significantly ameliorated with HEAM pretreatment. Brain derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) gene expression were accelerated by HEAM preadminstration. Molecular docking studies exhibited the highest binding affinity of chlorogenic acid towards acetylcholinesterase receptor with docking score -8.13. The current findings advocates that HEAM could be a strong neuroprotective agent against cognitive deficit associated with AD and its possible underlying mechanism might be improving brain cholinergic status through CREB-BDNF pathway as well as oxidative balance.

Neuroprotective Effects of Red Ginseng Saponins in Scopolamine-Treated Rats and Activity Screening Based on Pharmacokinetics.

Ginseng has been used to alleviate age-related dementia and memory deterioration for thousands of years. This study investigated the protective effect of red ginseng saponins against scopolamine-induced cerebral injury. Meanwhile, pharmacokinetics of ginsenosides in normal and scopolamine-treated rats were compared. After scopolamine injection, glutathione, catalase and superoxide dismutase levels were significantly decreased when compared with control group. Compared with SA group, pretreatment of rats with red ginseng saponins could increase glutathione, catalase and superoxide dismutase level. Treatment with red ginseng saponins significantly decreased malondialdehyde level. In the pharmacokinetic analysis, a pattern recognition analysis method was used to investigate the pharmacokinetics of the absorbed compounds in blood. The pharmacokinetic parameters of Rg1, Rg2, Rh3, Rg5 and Rk1 in model group had higher area under the curve (AUC), mean residence time (MRT) and peak plasma concentration (Cmax) values; area under the curve (AUC) values and peak plasma concentration (Cmax) of model group was significantly different from that of normal group (p < 0.05). The Cmax value of Rk3, Rh1, Rh2 and Rh4 in model group was higher than normal group, but their AUC values were not significantly different. There was no significantly difference in time at Cmax (Tmax), AUC and Cmax values of Rb1, Rb2 Re, Rc, Rd and Rf between the model and normal group. 16 ginsenosides were grouped into three separate clusters according to principal component analysis (PCA) score plot based on pharmacokinetic data. The results suggested red ginseng saponins have significant protective effect against scopolamine-induced memory deficit and scopolamine-induced rats could lead to the changes of pharmacokinetic behaviors of ginsenosides.

Taurine Prevents Passive Avoidance Memory Impairment, Accumulation of Amyloid-β Plaques, and Neuronal Loss in the Hippocampus of Scopolamine-Treated Rats

One of the hallmarks of Alzheimer’s disease (AD) is extracellular deposition of amyloid-β peptides, particularly in the hippocampus. Despite the antioxidant properties of taurine, its neuroprotective potential against amyloid-β accumulation in scopolamine-induced AD model remain unclear. In such a model, we aimed to assess the effects of taurine on passive avoidance memory impairment, accumulation of congophilic amyloid-β plaques, and neuronal density in the rat hippocampus. Rats, except the control group, were i.p. injected with 3 mg/kg scopolamine. The pretreated and treated groups were also injected with taurine (25, 50, or 100 mg/kg/day, i.p.) for 14 days before or after scopolamine introduction. All rats (except the control group) were tested for the passive avoidance reaction 24 h after the last drug injection. For histological analysis, hippocampal sections were stained with Congo red and cresyl violet. Administration of taurine for 14 days, both before and after scopolamine injection, significantly alleviated passive avoidance memory impairment. Pretreatment with taurine in any of the mentioned dosages significantly decreased the number of congophilic amyloid-β plaques in the rat hippocampus, including the CA3 area. Taurine also reduced scopolamine-induced neuronal loss in the hippocampus.

Corneal autophagy and ocular surface inflammation: A new perspective in dry eye

Dry eye disease (DED), a multifactorial ocular surface disorder affecting millions of individuals worldwide, is characterized by inflammation and damage to the ocular surface. It is unclear whether corneal autophagy participates in ocular surface inflammation observed in DED. To test this involvement, dry eye (DE) was induced in female C57BL/6 mice housed in a controlled environment by subcutaneous injection of scopolamine. Expression of the autophagy-related proteins LC3B and ATG5 and activation of autophagy were detected in the corneas of these mice. Treatment with LYN-1604, an activator of autophagy, alleviated the clinical indications in DE mice, including tear production and corneal fluorescence staining. LYN-1604 also reduced the corneal levels of inflammatory response products, including tumor necrosis factor alpha (TNF-α) and matrix metalloproteinases-3 and -9. By contrast, treatment of DE mice with the autophagy inhibitor 3-MA, exacerbated the clinical indications of DE and increased the levels of inflammatory response products. This is the first study to show that autophagy could regulate the level of ocular surface inflammation, suggesting that agents that regulate autophagy could relieve ocular surface inflammation and treat DED.

Aniracetam does not improve working memory in neurologically healthy pigeons.

Understanding the effects of cognitive enhancing drugs is an important area of research. Much of the research, however, has focused on restoring memory following some sort of disruption to the brain, such as damage or injections of scopolamine. Aniracetam is a positive AMPA-receptor modulator that has shown promise for improving memory under conditions when the brain has been damaged, but its effectiveness in improving memory in neurologically healthy subjects is unclear. The aim of the present study was to examine the effects of aniracetam (100mg/kg and 200 mg/kg) on short-term memory in “neurologically healthy” pigeons. Pigeons were administered aniracetam via either intramuscular injection or orally, either 30 or 60 minutes prior to testing on a delayed matching-to-sample task. Aniracetam had no effect on the pigeons’ memory performance, nor did it affect response latency. These findings add to the growing evidence that, while effective at improving memory function in models of impaired memory, aniracetam has no effect in improving memory in healthy organisms.

Rebamipide ophthalmic solution modulates the ratio of Thelper cell 17/regulatory T cells in dry eye disease mice.

The aim of the present study was to confirm the effect of 2% rebamipide ophthalmic solution on a scopolamine-induced dry eye (DE) mouse model, and to investigate its effect on the ratio of T helper cell 17 (Th17)/regulatory T cell (Treg) numbers. C57BL/6 mice received subcutaneous injections of scopolamine and were exposed to a low-humidity environment in order to establish a DE model. Rebamipide eye drops (2%) administered four times daily for 2 weeks, significantly reduced the corneal staining scores and increased the tear film breakup time and tear production in the DE mice. Pathologically, the rebamipide restored the histological changes induced by DE in the cornea, conjunctiva and lacrimal gland. At a molecular level, it downregulated pro-inflammatory and upregulated anti-inflammatory cytokines in the conjunctiva and lacrimal gland. Furthermore, the increased Th17 and Treg levels were restored following treatment with rebamipide. In conclusion, the anti-inflammatory and Th17/Treg balance-preserving effects of rebamipide may contribute to the treatment of DE in mice.

Comparison of donepezil and riluzole in improving spatial memory of male Wistar rats

Purpose: Alzheimer’s disease (AD) is a degenerative brain disorder and the major cause of dementia and cognitive deficits in the elderly. Riluzole modulates glutamate concentration and improves memory performance in aged rats and may be of benefit in AD. Donepezil is a cholinesterase inhibitor that is used for the treatment of mild-to-moderate AD. In this study, we compared their effects on attenuation of learning and memory deficits in a rat model of AD. Materials and Methods: Scopolamine injection for 14 consecutive days induced memory impairment. Effect of riluzole on this impaired memory was evaluated by Morris water maze protocols: accusation phase and probe trial test. Adult male Wistar rats (250–300g) were trained for 4 consecutive days, 24 hours after last scopolamine injection. Spatial memory and learning index (%) were measured depending on the time taken to find the platform and the time utilized in the target quadrant (Q2). The time/distance was measured by the computer. Results were analyzed by one-way analysis of variance and Tukey post hoc. Results: Riluzole was effective in the treatment of memory impairment of scopolamine-injected group. The riluzole-treated group, on test day, showed better spatial memory rather than scopolamine-treated group. Besides, learning index (%) improvement was significantly higher in the riluzole-treated group, rather than scopolamine-injected group. Conclusion: It can be concluded that riluzole administration at the same time with scopolamine injection or after it causes marked improvements in learning index during training days and the spatial memory on the test day. Therefore, this study strengthens the hypothesis that acute riluzole treatment is capable of treatment of diseases related to memory impairment such as AD.

Effect of ethanolic extract of leaves of Solanum trilobatum on scopolamine-induced memory impairment in Sprague Dawley rats

Objective: The objective of the study is to determine the effect of ethanolic extract of leaves of Solanum trilobatum (EEST) on scopolamine-induced memory impairment in Sprague Dawley (SD) rats. Materials and Methods: The leaves of S. trilobatum were extracted with ethanol and used for the study. The SD rats were divided into six groups each consist of six animals, namely normal control; scopolamine control; donepezil treated 3 mg/kg; and EEST treated 100, 200, and 400 mg/kg, respectively. Except normal control, all other animals were administered with intraperitoneal injection of scopolamine (1 mg/kg body weight) for 21 days to induce memory impairment. Donepezil and EEST were administered once daily through oral gavage for 21 consecutive days. On prestudy, 7th, 14th, and 21st days of the experiment, the animals' locomotor activity, muscle grip strength and escape latency time (ELT) were measured. At the end of the study, blood samples were collected from all the animals and they were sacrificed; the organs such as brain, liver, lung, heart, kidney, and stomach were harvested, and absolute organ weight was measured. Blood samples were used for the biochemical analysis. Results: The rats treated with EEST 100, 200, and 400 mg/kg did not show any change in locomotor activity and grip strength and significantly reduced motor resistance. The animals treated with donepezil showed a significant reduction in ELT. The animals treated with EEST 100 and 200 mg/kg showed significant increases in ELT, whereas animals treated with EEST 400 mg/kg did not show significant changes in ELT compared with that of prestudy. At the end of the study, EEST-treated animals did not show significant changes in biochemical parameters, whereas donepezil-treated animals showed a significant increase in cholesterol level compared with control animals. Furthermore, EEST did not affect regular body weight gain, absolute and relative organ weight. Conclusion: EEST did not show neuroprotective effect at lower doses in rats, but the high dose (400 mg/kg) prevented scopolamine-induced memory impairment, and this effect is not significant when compared with standard donepezil.

Anti-amnesic and Cognitive Enhancing Effects of Ethanol Leaf Extract of Milicia Excelsa (Moraceae) in Mice

Objective: We investigated the anti-amnesic and cognitive enhancing effects of the ethanol leaf extract of Milicia excelsa in mice. Methodology: Amnesia was induced by intraperitoneal injection of scopolamine (0.4mg/kg) in Morris Water Maze; scopolamine (1mg/kg) on Y-maze test; scopolamine (0.4mg/kg) and diazepam (1mg/kg) on elevated plus maze. The effect of the extract on learning and memory of young and aged mice was also investigated on the elevated plus maze. The probable mechanism of cognitive enhancing effects of the extract was investigated using acetylcholinesterase enzyme and nitric oxide assays. Results: The extract significantly (p<0.05) attenuated amnesia induced by scopolamine in Morris water maze; reversed amnesia induced by scopolamine and diazepam on elevated plus maze; increased spontaneous alternation behaviour without modifying locomotor activities on Y-maze test; inhibited natural age-induced learning and memory impairment of aged mice while the learning and memory of young mice were significantly (p<0.05) enhanced on elevated plus maze. The extract also significantly (p<0.05) reduced acetylcholinesterase enzyme activity and increased nitric oxide concentration in the mice whole brain. Conclusion: This study, therefore, concluded that ethanol leaf extract of Milicia excelsa may possess anti-amnesic and memory enhancing effects which may involve cholinergic and nitergic pathways.

Ginkgo biloba Extract Decreases Scopolamine-Induced Congophilic Amyloid Plaques Accumulation in Male Rat's Brain

Background: Scopolamine can induce amyloid β accumulation, oxidative stress, synaptic loss, and learning/memory deficit as seen in Alzheimer’s disease. Ginkgo biloba extract increases neurogenesis and suppresses the happening of pathological processes and cognitive decline. Objectives: Herein, we explored the effect of Ginkgo biloba extract on scopolamine-induced congophilic amyloid plaque accumulation and neurons density in the rats’ brain. Methods: Ginkgo biloba extract (40 and 80 mg/kg/day) was injected daily intraperitoneally for seven days before and after the scopolamine injection (3 mg/kg) in protective and treatment group rats. At the end of the experiments, the rats’ brains were removed and fixed in 4% paraformaldehyde. After histological processing, Congo red staining was used to assess amyloid plaques while cresyl violet staining was employed to determine the neuron density. Results: The administration of scopolamine led to increased congophilic amyloid plaque density in the hippocampus and cingulate cortex of the rats. Pretreatment with Ginkgo biloba extract significantly decreased congophilic amyloid plaque numbers in the hippocampus and cingulate cortex. In addition, scopolamine could reduce the hippocampal and cingulate cortex neuron numbers compared to the control group rats. However, Ginkgo biloba extract increased the hippocampal and cingulate cortex neuron numbers before and after the injection of scopolamine. Conclusions: Our results showed that Ginkgo biloba extract could play protective roles against some scopolamine-induced Alzheimer’s disease-like pathologic dysfunctions, including amyloid β accumulation and neuronal loss, suggesting that treatment with Ginkgo biloba extract might be a promising prophylactic target for Alzheimer’s disease.

Diosmin is neuroprotective in a rat model of scopolamine-induced cognitive impairment.

Scopolamine, a muscarinic cholinergic receptor antagonist, is used as a standard pharmaceutical model for inducing cognitive impairment in animals. Several cognitive behaviors, such as motor function, anxiety, short-term memory, attention are affected by injections of scopolamine. In this study, we have assessed the effects of administration of the diosmin (DM, 50 and 100 mg/kg), before injection of 0.4 mg/kg of scopolamine on memory and motor function, the hippocampal dentate gyrus (DG) electrophysiological activity as well as brain inflammation. Eighty male rats were randomly divided into five groups (Control, Veh + scopolamine, DM (50) + scopolamine and DM (100) + scopolamine, donepezil (DP) + scopolamine, n = 16). Scopolamine (0.4 mg/kg, i.p.) is used, in order to induce an animal model of cognitive impairment. Rats pretreated with doses of 50 and 100 mg/kg of DM, 3 mg/kg of DP and/or normal saline for 7 days, before injection of scopolamine. Long-term potentiation (LTP) recording was done for electrophysiological activity assessment. Passive avoidance task (PAT), rotarod and spatial memory tests were evaluated, using a shuttle box, rotarod apparatus and Morris water maze (MWM), respectively. Results indicated that DM at doses of 50 and 100 mg/kg, significantly reversed the LTP (amplitude and slope) impairment of the hippocampal DG neurons, induced by scopolamine. Also, DM at doses of 50 and 100 mg/kg increased the percent of the total time that animals spent in goal quarter, the step-through latency (s) and bar latency time in an animal model of cognitive impairment (p < 0.01 and p < 0.001), respectively. The concentrations of TNF-α in hippocampus of the DM and donepezil groups was significantly lower than the Veh + scopolamine group (p < 0.01). This study revealed that the DM is effective in preventing the disruption of synaptic plasticity and cognitive impairments, induced by scopolamine. The positive effects of DM may be mediated through a decline in the TNF- α concentrations in hippocampus as a pro-inflammatory cytokine. Thus, the acquired results suggested that the DM can be used, as a useful and suitable agent for memory restoration, in the treatment of dementia, seen in elderlies.

Activation of Dendritic Cells in Dry Eye Mouse Model.

The immune system plays a major role in the pathogenesis of dry eye diseases (DED), and dendritic cells (DCs) are known to be important initiators of acquired immunity. Thus, the purpose of this study was to determine the contribution of DCs to the development of DED. Mouse dry eye model was induced by subcutaneous injections of scopolamine and was euthanized at the baseline, and 2, 4, and 7 days postinjection. The activation of the DCs was determined by the mixed leukocyte reaction (MLR), and the number of activated CD86+ DCs in the lymph nodes was determined by flow cytometry. Upregulation of cytokines in the culture supernatant of MLR was determined by ELISA. Significantly increased superficial corneal punctate lesions and decreased number of goblet cells in the conjunctiva were observed in scopolamine-injected mice. The number of activated CD86+ DCs was significantly increased in the cervical lymph nodes but not in the inguinal lymph nodes of the dry eye mice. The stimulatory activity of the DCs derived from the cervical lymph nodes of dry eye mice was significantly higher than that of control mice, and upregulations of IL-17, IL-2, and IL-4 were observed in the culture supernatant of MLR. These results indicate that the DCs of the cervical lymph nodes were activated by the scopolamine injections. Our results indicate that DCs in our dry eye model were sufficiently activated to stimulate the T cells that participate in the onset and progression of DED.

Amelioration of Cognitive Deficit by Embelin in a Scopolamine-Induced Alzheimer's Disease-Like Condition in a Rat Model.

Embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone) is one of the active components (2.3%) found in Embelia ribes Burm fruits. As determined via in vitro AChE inhibition assay, embelin can inhibit the acetylcholinesterase enzyme. Therefore, embelin can be utilized as a therapeutic compound, after further screening has been conducted for its use in the treatment of Alzheimer’s disease (AD). In this study, the nootropic and anti-amnesic effects of embelin on scopolamine-induced amnesia in rats were evaluated. Rats were treated once daily with embelin (0.3 mg/kg, 0.6 mg/kg, 1.2 mg/kg) and donepezil (1 mg/kg) intraperitoneally (i.p.) for 17 days. During the final 9 days of treatment, a daily injection of scopolamine (1 mg/kg) was administered to induce cognitive deficits. Besides that, behavioral analysis was carried out to assess the rats’ learning and memory functions. Meanwhile, hippocampal tissues were extracted for gene expression, neurotransmitter, and immunocytochemistry studies. Embelin was found to significantly improve the recognition index and memory retention in the novel object recognition (NOR) and elevated plus maze (EPM) tests, respectively. Furthermore, embelin at certain doses (0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg) significantly exhibited a memory-enhancing effect in the absence of scopolamine, besides improving the recognition index when challenged with chronic scopolamine treatment. Moreover, in the EPM test, embelin treated rats (0.6 mg/kg) showed an increase in inflection ratio in nootropic activity. However, the increase was not significant in chronic scopolamine model. In addition, embelin contributed toward the elevated expression of BDNF, CREB1, and scavengers enzymes (SOD1 and CAT) mRNA levels. Next, pretreatment of rats with embelin mitigated scopolamine-induced neurochemical and histological changes in a manner comparable to donepezil. These research findings suggest that embelin is a nootropic compound, which also possesses an anti-amnesic ability that is displayed against scopolamine-induced memory impairment in rats. Hence, embelin could be a promising compound to treat AD.

Levels of Thyroid Hormones and Indices of Energy Metabolism in the Cerebral Cortex of Rats with Experimental Alzheimer’s Disease

The study was carried out on 30 mature WAG rats, 15 intact control animals and 15 rats with modeled Alzheimer’s disease (AD) induced by course injections of scopolamine (27 days, 1 mg/kg, i.p. daily). The contents of ATP, glucose, pyruvate, and lactate were measured spectrophotometrically in homogenates of the brain cortex of the animals. The levels of TSH, T3, and T4 in blood serum and those of T3 and T4 in cortex homogenates were estimated using ELISA. The activities of pyruvate dehydrogenase, creatine phosphokinase, and key enzymes of the tricarboxylic acid cycle (TCA) were measured in the mitochondria using a spectrophotometric technique. It was found that the content of T3 in the brain cortex of rats was much lower than in the controls against the background of higher T4 concentrations, which was indicative of the development of local hypothyroidism in the brain. The increased activity of pyruvate dehydrogenase against the background of low activities of TCA cycle enzymes in brain homogenates was observed. The decreased creatine kinase activity and low ATP contents were also found. Local hypothyroidism in the brain cortex is believed to be one of the significant factors inducing the development of strong energy deficiency and reducing the activity of Krebs cycle enzymes. Consequently, this contributes to the death of neurons in experimental AD in rats.

Gender dependent contribution of muscarinic receptors in memory retrieval under sub-chronic stress

Stress induces retrograde amnesia in humans and rodents. Muscarinic antagonism under normal physiological conditions causes gender dependent impairment in episodic memory retrieval. We aimed to explore the gender dependent role of muscarinic receptors in memory retrieval under sub-chronic stress condition. Male and female mice were trained for Morris water maze test and contextual fear conditioning, followed by 3 h restraint stress per day for five days. Stress was either given alone or in combination with a daily subcutaneous injection of scopolamine (1 mg/kg) or donepezil (1 mg/kg). Control mice were given saline without any stress. Sub-chronic stress (induced for five days) impaired spatial memory retrieval in males (P < 0.005) but not in females (P > 0.05). Stress induced spatial memory recall deficit in male mice was independent of muscarinic receptor activity (P > 0.05). However, stress induced contextual fear memory recall impairment was reversed by donepezil treatment in male (P < 0.005) and female (P < 0.0001) mice. These findings suggest that differential role of muscarinic activity in retrieving different types of memories under stress depends on gender of subjects.

Astrocytes activation contributes to the antidepressant-like effect of ketamine but not scopolamine

Depression is a common, debilitating mood disorder, but currently available antidepressants have several major drawbacks. Both ketamine and scopolamine attract more and more attention due to their rapid and sustained antidepressant activities. However, the molecular and cellular mechanism that underlies the therapeutic action of ketamine and scopolamine still remain to be elucidated. Considering the importance of astrocytes in the development of depression, we hypothesized that the activation of astrocyte may play a vital role in the antidepressant effects of ketamine and scopolamine. In the present study, the expression of fibrillary acidic protein (GFAP) was detected to evaluate the activation of astrocyte after single injection of ketamine and scopolamine in respective efficient doses. Behavioral tests used to assess antidepressant-like effects were forced swim test (FST) and tail suspension test (TST). Fluorocitrate, a well-established astrocyte inactivator, was adopted to inhibit the activation of astrocyte. The results demonstrated that ketamine, but not scopolamine, could increase significantly the expression of GFAP in hippocampus. In addition, inhibition of astrocyte abolished the antidepressant-like effects of ketamine, but not scopolamine in the FST and TST. It is suggested that activated astrocyte plays a vital role in the antidepressant activities of ketamine rather than scopolamine. These findings may be important for the understanding of the role of astrocyte in depression and antidepressants, especially rapid antidepressants.

Moringa oleifera Seed Extract Alleviates Scopolamine-Induced Learning and Memory Impairment in Mice.

The extract of Moringa oleifera seeds has been shown to possess various pharmacological properties. In the present study, we assessed the neuropharmacological effects of 70% ethanolic M. oleifera seed extract (MSE) on cognitive impairment caused by scopolamine injection in mice using the passive avoidance and Morris water maze (MWM) tests. MSE (250 or 500 mg/kg) was administered to mice by oral gavage for 7 or 14 days, and cognitive impairment was induced by intraperitoneal injection of scopolamine (4 mg/kg) for 1 or 6 days. Mice that received scopolamine alone showed impaired learning and memory retention and considerably decreased cholinergic system reactivity and neurogenesis in the hippocampus. MSE pretreatment significantly ameliorated scopolamine-induced cognitive impairment and enhanced cholinergic system reactivity and neurogenesis in the hippocampus. Additionally, the protein expressions of phosphorylated Akt, ERK1/2, and CREB in the hippocampus were significantly decreased by scopolamine, but these decreases were reversed by MSE treatment. These results suggest that MSE-induced ameliorative cognitive effects are mediated by enhancement of the cholinergic neurotransmission system and neurogenesis via activation of the Akt, ERK1/2, and CREB signaling pathways. These findings suggest that MSE could be a potent neuropharmacological drug against amnesia, and its mechanism might be modulation of cholinergic activity via the Akt, ERK1/2, and CREB signaling pathways.

Dietary Supplementation of Almond Prevents Oxidative Stress by Advocating Antioxidants and Attenuates Impaired Aversive Memory in Male Rats.

Scopolamine, an anti-muscarinic agent, has been shown to induce amnesia and oxidative stress similar to that observed in the older age. The present study was designed to determine the relationship between the oxidative status and memory improvement in scopolamine injected rats pre-administered with almonds. Rats (n = 8) in the almond group were administered orally with 400mg/kg almond suspension for 28days daily before the intraperitoneal injection of scopolamine (0.5mg/kg). Passive avoidance task (PAT) was used to assess memory function at the end of treatment. The present study revealed that scopolamine injection significantly impaired the memory function in rats pre-treated with saline which was accompanied by increased oxidative stress as evident by increased brain malondialdehyde (MDA) levels and reduced activities of antioxidant enzymes as compared to healthy controls. Pre-treatment with almond significantly ameliorated scopolamine-induced oxidative stress and memory dysfunction. These findings suggest that dietary supplementation with almonds may have a beneficial effect in reducing the risk of oxidative stress-induced memory loss and delaying or preventing the onset of age-related memory impairment.

Scopolamine-Induced Memory Impairment Is Alleviated by Xanthotoxin: Role of Acetylcholinesterase and Oxidative Stress Processes.

Xanthotoxin, popularly occurring furanocoumarin, which can be found in plants from the Apiaceae family, was isolated from fruits of Pastinaca sativa L. by mean of high-performance countercurrent chromatography, and its effects on the scopolamine-induced cognitive deficits in male Swiss mice using the passive avoidance (PA) test were evaluated. To measure the acquisition of memory processes, xanthotoxin (1, 2.5, 5 mg/kg) was administered 30 min before PA test and scopolamine was administered 10 min after xanthotoxin. To measure the consolidation of memory processes, xanthotoxin (1 and 2.5 mg/kg) was injected immediately after removing the mouse from the apparatus and 10 min after scopolamine was administered. In subchronic experiments, mice were injected with xanthotoxin (1 mg/kg) or saline, 6 days, twice daily. At 24 h after the last injection of the drugs, the hippocampus and the prefrontal cortex were removed for biochemical assays. The results demonstrated that either single (2.5 and 5 mg/kg) or repeatable (1 mg/kg) administration of xanthotoxin significantly increased index of latency (IL) in both acquisition and consolidation of memory processes, showing some procognitive effects. The behavioral tests also showed that an acute (2.5 mg/kg) and subchronic (1 mg/kg) administration of xanthotoxin prevent memory impairment induced by injection of scopolamine (1 mg/kg). Observed effects could be due to the inhibition of acetylcholinesterase activities and amelioration of oxidative stress processes in the hippocampus and the prefrontal cortex. It was suggested that xanthotoxin could show neuroprotective effect in scopolamine-induced cognitive impairment connected to cholinergic neurotransmission and oxidative stress in the brain structures.

Vitamin E can compensate the density of M1 receptors in the hippocampus of scopolamine-treated rats.

M1 muscarinic receptor plays afundamental role in memory and is closely associated with Alzheimer's disease (AD); it has long been assumed as atherapeutic goal. By activating of the cholinergic receptor vitamin E helps with memory retention. But effects of vitamin E on density of M1 muscarinic receptor-immunoreactive (ir) neurons remain poorly understood. The present research aimed to examine the chronic administration effect of vitamin E against scopolamine-induced memory loss and the number of M1 muscarinic receptor-ir neurons of the hippocampus in male rats. Randomly, 42 adult male Wistar rats were divided to six groups: control, Sham-saline: receiving scopolamine + saline, Sham-sesame oil: receiving scopolamine + sesame oil and three experimental groups: receiving scopolamine + vitamin E with different doses (25, 50, and 100 mg/kg/day, i.p.) for 14 days. The passive avoidance task was used for the memory test. Twenty-four hours after behavioral tests, rats' brains were taken and fixed, and after tissue processing, sections were stained using the immunohistochemical technique for M1 muscarinic receptor-ir neurons and cresyl violet for neurons. The injection of scopolamine to rats caused memory impairment and vitamin E treatment could ameliorate it. In the scopolamine-treated groups, the number of CA1 and CA3 pyramidal and dentate gyrus (DG) granular neurons was decreased significantly as compared to the control group. Vitamin E treatment significantly increased neuron numbers in the CA1 and CA3 areas of the hippocampus and DG area. Treatment with vitamin E for 14 days could compensate the loss of M1 muscarinic receptor-immunoreactive neuron numbers induced by scopolamine in the hippocampus. The most effective vitamin E dose was 50 mg/kg/day in this study. In conclusion, vitamin E can compensate the neuronal loss in the hippocampal formation and also it can raise the density of M1 receptor-ir muscarinic neurons after an injection of scopolamine.