Zehra Batool

A high dose of short term exogenous d-galactose administration in young male rats produces symptoms simulating the natural aging process

AIMS D-Galactose (D-gal) induced accelerated senescence has been used to develop an aging model for brain. Previously, long term administration of a wide range of doses has been used for this purpose. In the present study we investigate whether short term administration of a high dose of D-gal in rats induces significant signs and symptoms similar to natural aging. MAIN METHODS Young rats were injected intraperitoneally with D-gal at a dose of 300 mg/ml/kg for one week. Behavioral analysis for depression and anxiety like symptoms were monitored by forced swim test (FST) and light/dark transition (LDT) test. Assessment of memory was done using the Morris water maze (MWM), passive avoidance test (PAT) and elevated plus maze (EPM) test. Biochemical analysis was done for estimation of antioxidant enzymes and acetylcholinesterase. Determination of brain biogenic amines was performed by HPLC-EC. KEY FINDINGS Short term administration of D-gal significantly altered behavioral, biochemical and neurochemical responses in rats. D-Gal injected rats exhibited depressogenic and anxiogenic behaviors while memory was also significantly impaired in these rats. Brain lipid peroxidation and superoxide dismutase activity were significantly increased while catalase and glutathione peroxidase decreased. Increased activity of acetylcholinesterase was also exhibited by D-gal injected rats while brain biogenic amines were significantly decreased. Food intake and growth rate were however comparable in both groups. SIGNIFICANCE Together the behavioral, biochemical and neurochemical impairments following the high dose of D-gal suggest that symptoms similar to natural aging may be developed in rats in as early as one week.

Pretreatment with curcumin attenuates anxiety while strengthens memory performance after one short stress experience in male rats

It is observed that memories are more strengthened in a stressful condition. Studies have also demonstrated an association between stressful events and the onset of depression and anxiety. Considering the nootropic, anxiolytic and antidepressant-like properties of curcumin in various experimental approaches, we appraised the beneficial effects of this herb on acute immobilization stress-induced behavioral and neurochemical alterations. Rats in test group were administrated with curcumin (200mg/kg/day), dissolved in neutral oil, for 1 week. Both control and curcumin-treated rats were divided into unstressed and stressed groups. Rats in the stressed group were subjected to immobilization stress for 2h. After stress, the animals were subjected to behavioral tests. Immobilization stress induced an anxiogenic behavior in rats subjected to elevated plus maze test (EPM). Locomotor activity was also significantly increased following the acute immobilization stress. Pre-administration of curcumin prevented the stress-induced behavioral deficits. Highest memory performance was observed in stressed rats that were pre-treated with curcumin in Morris water maze (MWM). Brain malondialdehyde (MDA) levels, catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and acetylcholinesterase (AChE) activities were also estimated. Present study suggests a role of antioxidant enzymes in the attenuation of acute stress induced anxiety by curcumin. The findings therefore suggest that supplementation of curcumin may be beneficial in the treatment of acute stress induced anxiety and enhancement of memory function.

Repeated administration of almonds increases brain acetylcholine levels and enhances memory function in healthy rats while attenuates memory deficits in animal model of amnesia.

Dietary nutrients may play a vital role in protecting the brain from age-related memory dysfunction and neurodegenerative diseases. Tree nuts including almonds have shown potential to combat age-associated brain dysfunction. These nuts are an important source of essential nutrients, such as tocopherol, folate, mono- and poly-unsaturated fatty acids, and polyphenols. These components have shown promise as possible dietary supplements to prevent or delay the onset of age-associated cognitive dysfunction. This study investigated possible protective potential of almond against scopolamine induced amnesia in rats. The present study also investigated a role of acetylcholine in almond induced memory enhancement. Rats in test group were orally administrated with almond suspension (400 mg/kg/day) for four weeks. Both control and almond-treated rats were then divided into saline and scopolamine injected groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM) and novel object recognition (NOR) task. Cholinergic function was determined in terms of hippocampal and frontal cortical acetylcholine content and acetylcholinesterase activity. Results of the present study suggest that almond administration for 28 days significantly improved memory retention. This memory enhancing effect of almond was also observed in scopolamine induced amnesia model. Present study also suggests a role of acetylcholine in the attenuation of scopolamine induced amnesia by almond.

Increased 5-HT Levels Following Repeated Administration of Nigella sativa L. (Black Seed) Oil Produce Antidepressant Effects in Rats.

The seeds of Nigella sativa L., commonly known as black seed or black cumin, and its extracts are used in folk medicine in the Middle East and in Asian countries for the promotion of good health and as a remedy for many ailments. These seeds have many acclaimed medicinal properties such as broncho-dilatory, immunopotentiating, analgesic, anti-inflammatory, and hypotensive. In the present study, the antidepressant activity following the repeated administration of Nigella sativa L. oil has been monitored using the forced swim test. Rats treated with Nigella sativa L. oil exhibited a significant increase in struggling time after oral administration of Nigella sativa L. oil (0.1 ml/kg/day) for four weeks. Nigella sativa L. oil increased brain 5-HT levels and decreased 5-HT turnover (5-HT/5-HIAA ratio). Levels of tryptophan increased significantly in the brain and plasma following the repeated administration of Nigella sativa L. oil. Nigella sativa L. oil showed a potential antidepressant-like effect.

Decreased Hippocampal 5-HT and DA Levels Following Sub-Chronic Exposure to Noise Stress: Impairment in both Spatial and Recognition Memory in Male Rats

Mankind is exposed to a number of stressors, and among them noise is one which can cause intense stress. High levels of background noise can severely impair one’s ability to concentrate. The present study was aimed to investigate the effect of sub-chronic noise stress on cognitive behavior and hippocampal monoamine levels in male rats. The study was performed on 12 male Wistar rats, divided into two groups; the control and noise-exposed. The rats in the test group were subjected to noise stress, 4h daily for 15 days. Cognitive testing was performed by the Elevated Plus Maze test (EPM) and Novel Object Recognition test (NOR). HPLC-EC was used to determine hippocampal monoamine levels and their metabolites. The data obtained revealed a significant decrease in hippocampal serotonin (5-hydroxytryptamine; 5-HT) and dopamine (DA) levels, whereas turnover ratios of 5-HT and DA were significantly increased compared to the controls. Rats exposed to noise exhibited a significant decrement in spatial memory. A significantly decreased recognition index of rats exposed to noise as compared to the control was also observed in the NOR test. Results of the present findings suggest the role of decreased hippocampal 5-HT and DA in the impairment of cognitive function following noise exposure.

Nootropic and hypophagic effects following long term intake of almonds (Prunus amygdalus) in rats

INTRODUCTION Over a period of time researchers have become more interested in finding out the potential of various foods to maintain the general health and to treat diseases. Almonds are a very good source of many nutrients which may help to sharpen the memory and to reduce cardiovascular risk factors. OBJECTIVE The present study was conducted to evaluate the nootropic effects of almonds. Effect of oral intake of almond was also monitored on food intake and plasma cholesterol levels. METHODS Rats were given almond paste orally with the help of feeding tube for 28 days. Memory function in rats was assessed by Elevated Plus Maze (EPM) and Radial Arm Maze (RAM). Brain tryptophan, 5-HT and 5-HIAA were estimated at the end of the treatment by HPLC-EC method. RESULTS A significant improvement in learning and memory of almond treated rats compared to controls was observed. Almond treated rats also exhibited a significant decrease in food intake and plasma cholesterol levels while the change in growth rate (in terms of percentage) remained comparable between the two groups. Analysis of brain tryptophan (TRP) monoamines exhibited enhanced TRP levels and serotonergic turnover in rat brain following oral intake of almonds. CONCLUSION The findings show that almonds possess significant hypophagic and nootropic effects. Results are discussed in context of enhanced 5-HT metabolism following almond administration.

Naringenin-induced enhanced antioxidant defence system meliorates cholinergic neurotransmission and consolidates memory in male rats

Aims: Free radical mediated neurotoxicity is a leading cause of neurodegenerative disorders. Neurodegeneration due to oxidative stress can produce cognitive dysfunctions. Flavonoids and curcuminoids are naturally occurring polyphenolic compounds that display a variety of therapeutic importance against oxidative stress. Main methods: This study was designed to assess potential role of polyphenolic compounds in neurocognitive functions and prevention against oxidative stress. For this purpose, young rats were orally treated with naringenin (NAR), curcumin (CUR) and quercetin (QUE) at a dose of 50 mg/kg, 200 mg/kg and 50 mg/kg respectively for 16 days. At 4th day of drug administration cognitive functions were monitored by Morris water maze (MWM) test. In MWM cognitive functions in terms of learning acquisition (1 h after training), retention (24 h after training), memory extinction (4 days after training), and reconsolidation (8 and 12 days after training) were monitored. Biochemical and neurochemical analysis were done in whole brain. Key findings: Treatment of NAR, CUR and QUE significantly enhanced learning acquisition, memory retention and reconsolidation and prevented memory extinction. Treatment of NAR and QUE prevented the alteration of brain antioxidant defence system by enhancing antioxidant enzyme activities and increasing antioxidant compound concentration. Oxidative stress in terms of lipid peroxidation was significantly prevented in treated rats. Serotonergic and cholinergic improvement was also found in treated rats. Significance: The present study therefore provides biological evidence supporting the usefulness of these polyphenolic compounds in daily life for improvement of cognitive abilities and hence may have a potential role in the management of dementia and related disorders. Graphical abstract: Figure. No caption available.

Attenuation of stress induced memory deficits by nonsteroidal anti-inflammatory drugs (NSAIDs) in rats: Role of antioxidant enzymes

BACKGROUND Repeated stress paradigms have been shown to cause devastating alterations on memory functions. Stress is linked with inflammation. Psychological and certain physical stressors could lead to neuroinflammation. Inflammatory process may occur by release of mediators and stimulate the production of prostaglandins through cyclooxygenase (COX). Treatment with COX inhibitors, which restrain prostaglandin production, has enhanced memory in a number of neuroinflammatory states showing a potential function for raised prostaglandins in these memory shortfalls. In the present study, potential therapeutic effects of indomethacin and diclofenac sodium on memory in both unrestraint and restraint rats were observed. METHODS AND RESULTS Two components, long term memory and short term memory were examined by Morris water maze (MWM) and elevated plus maze (EPM) respectively. The present study also demonstrated the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on lipid peroxidation (LPO) and activities of antioxidant enzymes along with the activity of acetylcholinesterase (AChE). Results of MWM and EPM showed significant effects of drugs in both unrestraint and restraint rats as escape latency and transfer latency, in respective behavioral models were decreased as compared to that of control. This study also showed NSAIDs administration decreased LPO and increased antioxidant enzymes activity and decreased AChE activity in rats exposed to repeated stress. CONCLUSION In conclusion this study suggests a therapeutic potential of indomethacin and diclofenac against repeated stress-induced memory deficits.

Physical enrichment enhances memory function by regulating stress hormone and brain acetylcholinesterase activity in rats exposed to restraint stress

ABSTRACT To study the effects of stress on mental health activity is of great importance in neuropsychological studies as it may affect the lifelong performance related to brain and overall health and wellbeing of an individual. It is observed very often that exposure to stress during early life can alter the brain function which may reflect as cognitive disability. Impairment of memory is associated with increased oxidative stress which is due to enhanced production of free radicals that may lead to lipid peroxidation and disintegration of cell structure and functions. Exposure to enriched environment has shown to enhance spatial learning and memory, although the underlying mechanism covering the regulation of antioxidant capacity is limited. Here we investigated short and long term memory using Morris water maze before and after giving restraint stress procedure in rats exposed to social and physically enriched environment. Levels of malondialdehyde (MDA), activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and acetylcholinesterase (AChE) in brain tissue were estimated. Plasma corticosterone was also determined after decapitation. Results demonstrated that rats pre‐exposed to physical along with social enrichment showed improved short and long term memory as compared to control group. However, restraint stress exerted differential effects in socially and physically enriched groups. Reduced lipid peroxidation and decreased activity of SOD, GPx and AChE were observed in physically enriched rats subjected to stress as compared to stressed rats kept in social environment. Levels of corticosterone were also found to be significantly reduced in rats kept in physically enriched environment. This study shows the beneficial effects of environmental enrichment on learning and spatial memory by reducing oxidative stress via reducing lipid peroxidation and regulation of antioxidant enzymes in rats.

Role of Cyclooxygenase Inhibitors in Diminution of Dissimilar Stress-induced Depressive Behavior and Memory Impairment in Rats

Memory functions can be considerably affected by various life events and stress has shown to be a chief regulator. Different stress patterns have distinct effects on the overall functioning of the brain. Stress provokes inflammation not only in the periphery but also in the brain. Neuroinflammation causes alterations in neuronal structure and function, which eventually progress to the development of neurodegenerative diseases. Inflammatory reactions are modulated through communication between the nervous, endocrine and immune systems. An excessive release of stress hormones and changes in the neurotransmission system may cause cognitive impairments. The present study investigated dissimilar stress-related memory deficits and their diminution by non-steroidal anti-inflammatory drugs (NSAIDs). Treatment with cyclooxygenase inhibitors, which inhibit prostaglandin synthesis, has enhanced memory functions in a number of neuroinflammatory states. In this study, rats were exposed to a series of dissimilar stressors and behavioral parameters for depression and memory functions were examined. Corticosterone, serotonin (5-HT) and dopamine (DA) levels were also estimated. Results from the forced swim test, elevated plus maze test and Morris water maze test showed significant effects of NSAIDs. A significant decrease in plasma corticosterone and increased DA and 5-HT levels were observed in NSAID-treated dissimilar-stressed rats. This study demonstrates the therapeutic potential of NSAIDs for dissimilar stress-induced depressive behaviors and impaired memory functions and related hormonal and neurochemical changes in the rat brain.