Mitochondrial plasticity and synaptic plasticity crosstalk; in health and Alzheimer's disease.

Synaptic plasticity is believed to underlie the cellular and molecular basis of memory formation. Mitochondria are one of the main organelles involved in metabolism and energy maintenance as plastic organelles that change morphologically and functionally in response to cellular needs and regulate synaptic function and plasticity through multiple mechanisms, including ATP generation, calcium homeostasis, and biogenesis. An increased neuronal activity enhances synaptic efficiency, during which mitochondria's spatial distribution and morphology change significantly. These organelles build up in the pre-and postsynaptic zones to produce ATP, which is necessary for several synaptic processes like neurotransmitter release and recycling. Mitochondria also regulate calcium homeostasis by buffering intracellular calcium, which ensures proper synaptic activity. Furthermore, mitochondria in the presynaptic terminal have distinct morphological properties compared to dendritic or postsynaptic mitochondria. This specialization enables precise control of synaptic activity and plasticity. Mitochondrial dysfunction has been linked to synaptic failure in many neurodegenerative disorders, like Alzheimer's disease (AD). In AD, malfunctioning mitochondria cause delays in synaptic vesicle release and recycling, ionic gradient imbalances, and mostly synaptic failure. This review emphasizes mitochondrial plasticity's contribution to synaptic function. It also explores the profound effect of mitochondrial malfunction on neurodegenerative disorders, focusing on AD, and provides an overview of how they sustain cellular health under normal conditions and how their malfunction contributes to neurodegenerative diseases, highlighting their potential as a therapeutic target for such conditions.

Geraniol mitigates anxiety-like behaviors in rats by reducing oxidative stress, repairing impaired hippocampal neurotransmission, and normalizing brain cortical-EEG wave patterns after a single electric foot-shock exposure.

Anxiety-like conditions can interfere with daily activities as the adaptive mechanism fails to cope with stress. These conditions are often linked with increased oxidative stress, and abrupt neurotransmission and electroencephalography (EEG) wave pattern. Geraniol, a monoterpenoid, has antioxidant and anti-inflammatory activities, as well as brain-calming effects. Therefore, in this study, geraniol was tested for the potential anxiolytic effects in a rat model of anxiety. The rats were exposed to an electric foot shock (1 mA for 1 s) to develop anxiety-like symptoms. Treatment was carried out using geraniol (10 and 30 mg/kg) and the standard diazepam drug. The behavior of the rats was analyzed using the open field test, light-dark test, and social interaction test. Afterward, the rats were decapitated to collect samples for neurochemical and biochemical analyses. The cortical-EEG wave pattern was also obtained. The study revealed that the electric foot shock induced anxiety-like symptoms, increased oxidative stress, and altered hippocampal neurotransmitter levels. The power of low-beta and high-beta was amplified with the increased coupling of delta-beta waves in anxiety group. However, the treatment with geraniol and diazepam normalized cortical-EEG wave pattern and hippocampal serotonin and catecholamines profile which was also reflected by reduced anxious behavior and normalized antioxidant levels. The study reports an anxiolytic potential of geraniol, which can be further explored in future.

Insulin-like growth factor-1 (IGF-1) levels in multiple sclerosis patients: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls. METHODS: In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls. RESULTS: Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls. CONCLUSION: Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease.

Post-exposure self-recovery reverses oxidative stress, ameliorates pathology and neurotransmitters imbalance and rescues spatial memory after time-dependent aluminum exposure in rat brain.

Aluminum is a potent neurotoxin, responsible for memory impairment and cognitive dysfunction. The neurotoxic effect of aluminum on cognitive impairment is well documented, however, exposure to aluminum in a time-dependent manner and post-exposure self-recovery still needs to be elaborated. This research aimed to (1) study the time-dependent effect of aluminum exposure by administering a total dose of 5850 mg/kg of Al over two different time periods: 30 and 45 days (130 and 195 mg/kg of AlCl3 respectively), and (2) study 20 days post-exposure self-recovery effect in both aluminum-exposed groups by giving distilled water. Cognitive abilities were investigated through Morris water maze test and hole board test and compared in both exposure and recovery groups. Oxidative stress markers and neurotransmitter levels were measured for both exposure and recovery groups. To understand the mechanism of aluminum exposure and recovery, immunohistochemical analysis of synaptophysin (Syp) and glial fibrillary acidic protein (GFAP) was performed. Results showed cognitive dysfunction, oxidative stress-induced damage, reduced neurotransmitter levels, decreased immunoreactivity of Syp, and increased GFAP. However, these parameters showed a larger improvement in the recovery group where rats were given aluminum for 30 days period in comparison to recovery group followed by 45 days of aluminum exposure. These results suggest that restoration of cognitive ability is affected by the duration of aluminum exposure. The study findings provide us with insight into the adverse effects of aluminum exposure and can be utilized to guide future preventive and therapeutic strategies against aluminum neurotoxicity.

Naringenin, a Functional Food Component, Improves Motor and Non-Motor Symptoms in Animal Model of Parkinsonism Induced by Rotenone.

Parkinson's disease (PD) and other age-related neurodegenerative ailments have a strong link to oxidative stress. Bioflavonoid naringenin has antioxidant properties. The effects of pre- and post-naringenin supplementation on a rotenone-induced PD model were examined in this work. Naringenin (50 mg/kg, p.o.) was administered to rats for two weeks before the administration of rotenone in the pre-treatment phase. In contrast, rotenone (1.5 mg/kg, s.c.) was administered for eight days before naringenin (50 mg/kg, p.o.) was supplemented for two weeks in the post-treatment phase. During behavioral investigation, the motor and non-motor signs of PD were observed. Additionally, estimation of neurochemical and biochemical parameters was also carried out. Compared to controls, rotenone treatment substantially increased oxidative stress, altered neurotransmitters, and caused motor and non-motor impairments. Rotenone-induced motor and non-motor impairments were considerably reduced by naringenin supplementation. The supplementation also increased antioxidant enzyme activities and restored the changes in neurotransmitter levels. The findings of this work strongly imply that daily consumption of flavonoids such as naringenin may have a therapeutic potential to combat PD.

Electric foot-shock induces neurobehavioral aberrations due to imbalance in oxidative status, stress hormone, neurochemical profile, and irregular cortical-beta wave pattern in rats: A validated animal model of anxiety.

Neuropsychiatric disorders can be modeled on animals to investigate the neural mechanism underlying these disorders. Models of neuropsychiatric disorders, such as anxiety, basically aim to produce the signs and symptoms of human anxiety disorders in laboratory animals. Electric foot-shock is recommended to induce anxiety-like symptoms in rodents. For this purpose, however, a range of current intensities is available in the literature. The present study aims to modify the existing practices of generating anxiety-like symptoms through electric foot-shock by identifying an optimum current intensity and combining it with behavioral paradigms to produce a rat model of anxiety. Furthermore, the validity of the model was confirmed by checking the fulfillment of three validity criteria necessary for the development of any disease model including face validity, construct validity, and predictive validity. In the current study, after pre-testing, 1.0 mA electric intensity was selected to produce the model of anxiety. The results showed that the induction of 1.0 mA electric foot-shock induces abnormal behavioral effects which were similar to anxiety-like effects as evident by social interaction test, light-dark transition test, and open field test. Moreover, aberrations in the levels of the stress hormone, oxidative stress parameters, hippocampal neurotransmitter levels, and cortical-EEG wave pattern were also observed in the rat model of anxiety which were successfully overcome using diazepam. In conclusion, the outcome of our study suggests that electric foot-shock can be an adequate stressor to produce a validated animal model of anxiety and this model can be confidently used to identify and screen new and/or novel anxiolytics.

Natural remedies for Alzheimer's disease: A systematic review of randomized controlled trials.

Alzheimer's disease (AD) is the common type of dementia and is currently incurable. Existing FDA-approved AD drugs may not be effective for everyone, they cannot cure the disease nor stop its progression and their effects diminish over time. Therefore, the present review aimed to explore the role of natural alternatives in the treatment of AD. A systematic search was conducted using Ovid MEDLINE, CINAHL, Cochrane and PubMed databases and reference lists up to November 30, 2021. Only randomized control trials were included and appraised using the National Institute of Health framework. Data analysis showed that herbs like Gingko Biloba, Melissa Officinalis, Salvia officinalis, Ginseng and saffron alone or in combination with curcumin, low-fat diet, NuAD-Trail, and soy lecithin showed significant positive effects on AD. Moreover, combination of natural and pharmaceuticals has far better effects than only allopathic treatment. Thus, different herbal remedies in combination with FDA approved drugs are effective and more promising in treatment of AD.

Ameliorative effects of half-dose saffron and chamomile combination on Psycho-endocrinological changes in a diabetic murine model.

INTRODUCTION: Diabetes mellitus is a chronic metabolic disorder with an increasing prevalence worldwide. Reduction in blood insulin level alters brain function by inducing oxidative stress with changes in dopamine and norepinephrine neurotransmission, ultimately leading to neuropsychological symptoms. The efficacy of currently available psychotropic drugs is not satisfactory. Therefore, this study was conducted to explore the beneficial effects of a combination of the natural herbs, saffron and chamomile, in treating diabetes and its resultant neuropsychological effects using a rodent model of diabetes mellitus. METHOD: The rats were randomly divided in to eight groups (n = 10), healthy control (HC), diabetic control (DC) and six groups of diabetic rats treated with various concentrations and combinations of saffron and chamomile. Diabetic treatment groups individually received methanolic extract and water decoction of chamomile (30 mg/kg) and saffron (10mg/kg) and their combined half doses (saffron 5mg/kg and chamomile 15mg/kg) for two weeks. Open field test (OFT) and forced swim test (FST) were used to measure the anxiolytic and antidepressant effects of herbs, respectively. Finally, biochemical, and neurochemical estimations were made. RESULTS: The present study suggests the therapeutic effects of herbs especially in co-administrated decoction, against diabetes with improved antioxidant profile and enhanced levels of dopamine and norepinephrine. Anxiolytic and antidepressant effects were evident with improvements in the OFT and FST. Examination of the cortex of the diabetic group revealed cellular damage and tangle formation, which indicates advanced stages of dementia. CONCLUSION: This study shows that the use of a combination of saffron and chamomile improves diabetes control and reduces its related psychiatric effects.

Reversal of oxidative stress, cytokine toxicity and DNA fragmentation by quercetin in dizocilpine-induced animal model of Schizophrenia.

Quercetin, a polyphenolic compound found in a variety of plant products possesses various biological activities and beneficial effects on human health. Schizophrenia (SZ) is one of the neuropsychiatric disorders in human beings with rapid mortality and intense morbidity which can be treated with antipsychotics, but these commercial drugs exert adverse effects and have less efficacy to treat the full spectrum of SZ. The present study was conducted to evaluate neuroprotective effects of quercetin in the preventive and therapeutic treatment of SZ. Quercetin was administered as pre- and post-regimens at the dose of 50 mg/kg in dizocilpine-induced SZ rat model for two weeks. Rats were then subjected for the assessment of different behaviors followed by biochemical, neurochemical, and inflammatory marker analyses. The present findings revealed that quercetin significantly reverses the effects of dizocilpine-induced psychosis-like symptoms in all behavioral assessments as well as it also combats oxidative stress. This flavonoid also regulates dopaminergic, serotonergic, and glutamatergic neurotransmission. A profound effect on inflammatory cytokines and decreased %DNA fragmentation was also observed following the administration of quercetin. The findings suggest that quercetin can be considered as a preventive as well as therapeutic strategy to attenuate oxidative stress and cytokine toxicity, regulate neurotransmission, and prevent enhanced DNA fragmentation that can lead to the amelioration of psychosis-like symptoms in SZ.

Dose-dependent alteration of neurobehavioral activities by geraniol a component of essential oil: A study in rats.

Geraniol, a component of essential oil, is reported to have various pharmacological properties. The current study was conducted to demonstrate the dose-dependent neurobehavioral effects of geraniol. Rats were divided into 5 groups (n=7), comprising of control and four test groups for different doses of geraniol including 10, 30, 50 and 100 mg/kg. Geraniol was given for 15 days through intraperitoneal route. Following the administration, anxiety-, depression-like behaviors and memory function were evaluated. Extent of oxidative stress in rat's brain was also assessed by determining the levels of malondialdehyde and antioxidant enzymes activity. The present study revealed that low doses of geraniol produced more potent anxiolytic, antidepressant, nootropic, and antioxidant effects as compared to the higher doses. The findings highlight the dual characteristic of geraniol, acting as antioxidant at lower doses while at higher doses it produces pro-oxidant effects. The results are discussed in the context of dual characteristic of antioxidant compounds.

Neuroprotective role of a monoterpene (thymol) on diazepam induced withdrawal symptoms in rats.

Benzodiazepine administration is known to be related to tolerance and a withdrawal syndrome on sudden cessation. Thymol possesses multiple biological properties especially in the pathogenesis of different brain disorders. However, to the best of our knowledge there is no study that relates the use of thymol to benzodiazepine induced withdrawal symptoms. Therefore the aim of the current study was to investigate the usefulness of thymol in the treatment of benzodiazepine withdrawal syndrome in rats. Animals were divided into four groups, thymol (40mg/kg/ml), diazepam (4 mg/kg), thymol + diazepam and vehicle control group. The treatment was given for 14 days and then suddenly ceased. After 24 h animals were tested in different behavioral paradigms such as physical signs for withdrawal, marble burying test, inverted screen test, elevated plus maze, passive avoidance test and open field activity. The results of the present study revealed that co-administration of thymol significantly reduced the withdrawal symptoms induced by diazepam. Our results further suggest that administration of thymol not only ameliorates rebound anxiety associated with diazepam withdrawal but also improves motor and memory impairment in rats.

Quercetin exhibits potent antioxidant activity, restores motor and non-motor deficits induced by rotenone toxicity.

The rotenone-induced animal model of Parkinson's disease (PD) has been used to investigate the pathogenesis of PD. Oxidative stress is one of the main contributors of neurodegeneration in PD. Flavonoids have the potential to modulate neuronal function and combat various neurodegenerative diseases. The pre- and post-supplementation of quercetin (50 mg/kg, p.o) was done in rats injected with rotenone (1.5 mg/kg, s.c). After the treatment, behavioral activities were monitored for motor activity, depression-like behavior, and cognitive changes. Rats were decapitated after behavioral analysis and the brain samples were dissected out for neurochemical and biochemical estimation. Results showed that supplementation of quercetin significantly (p<0.01) restored rotenone-induced motor and non-motor deficits (depression and cognitive impairments), enhanced antioxidant enzyme activities (p<0.01), and attenuated neurotransmitter alterations (p<0.01). It is suggested that quercetin supplementation improves neurotransmitter levels by mitigating oxidative stress via increasing antioxidant enzyme activity and hence improves motor activity, cognitive functions, and reduces depressive behavior. The results of the present study showed that quercetin pre-supplementation produced more significant results as compared to post-supplementation. These findings show that quercetin can be a potential therapeutic agent to reduce the risk and progression of PD.

Therapeutic Potential of Curcumin in Reversing the Depression and Associated Pseudodementia via Modulating Stress Hormone, Hippocampal Neurotransmitters, and BDNF Levels in Rats.

Depressive state adversely affects the memory functions, especially in the geriatric population. The initial stage of memory deficits associated with depression is particularly called as pseudodementia. It is the starting point of memory disturbance before dementia. The purpose of this research was to study depression and its consequent pseudodementia. For this purpose 24 male albino Wistar rats were divided into four groups. Depression was induced by 14 days of chronic restraint stress (CRS) daily for 4 h. After developing a depression model, pattern separation test was conducted to monitor pseudodementia in rats. Morris water maze test (MWM) was also performed to observe spatial memory. It was observed that model animals displayed impaired pattern separation and spatial memory. Treatment was started after the development of pseudodementia in rats. Curcumin at a dose of 200 mg/kg was given to model rats for one week along with the stress procedure. Following the treatment with curcumin, rats were again subjected to the aforementioned behavioral tests before decapitation. Corticosterone levels, brain derived neurotrophic factor (BDNF) and neurochemical analysis were conducted. Model rats showed depressogenic behavior and impaired memory performance. In addition to this, high corticosterone levels and decreased hippocampal BDNF, 5-HT, dopamine (DA), and acetylcholine (ACh) levels were also observed in depressed animals. These behavioral biochemical and neurochemical changes were effectively restored following treatment with curcumin. Hence, it is suggested from this study that pseudodementia can be reversed unlike true dementia by controlling the factors such as depression which induce memory impairment.

Spirulina platensis reduces the schizophrenic-like symptoms in rat model by restoring altered APO-E and RTN-4 protein expression in prefrontal cortex.

AIMS: Schizophrenia (SZ) is recognized as a neuropsychiatric disorder in humans with accelerated mortality and profound morbidity followed with impairments in social as well as vocational functioning. Though various antipsychotics are being considered as approved treatment therapy for the psychotic symptoms of SZ but they also exert adverse effects and also lack efficacy in treating full spectrum of the disorder. Spirulina platensis (blue-green algae), a nutritional supplement, constitutes a variety of multi-nutrients and possesses a large number of neuroprotective activities. Therefore, present experimental work was designed to evaluate the neuroprotective effects of spirulina in ameliorating the psychosis-like symptoms in dizocilpine-induced rat model of SZ. MATERIALS AND METHODS: The spirulina was tested as preventive and therapeutic regimen at the dose of 180 mg/kg. After pre- and post-treatment with spirulina, rats were subjected to behavioral assessments followed by biochemical and neurochemical estimations. Biomarkers including APO-E, RTN-4, TNF-α, and IL-6 were also estimated using ELISA. KEY FINDINGS: Present results showed that administration of spirulina not only improved behavioral deficits induced by dizocilpine but it also regulates neurotransmission, oligodendrocyte dysfunction and APO-E over expression. Moreover, it also restores the immune response dysfunction by reducing inflammatory cytokines. SIGNIFICANCE: Thus, from present findings it may be suggested that spirulina aids in ameliorating the psychosis-like symptoms induced by dizocilpine in animal model possibly via regulation of neurotransmission and other biomarkers that are extensively used to uncover the etiopathology of SZ. Hence, blue-green algae can be used as an effective therapy for preventive or therapeutic measures in SZ.

Method for the identification of pharmacological intervention for the disruption of fear memory in PTSD-rat model.

A large portion of the human population is exposed to traumatic events once in their lifetime, 10% of which may undergo post-traumatic stress disorder (PTSD). It is a mental condition triggered by a traumatic event resulting in severe anxiety disorder which may severely affect the daily routine life of the individual. The patient expresses the aversive memory by recalling any fear event related to the traumatic experience. The disruption of fear memory related to fear event is one of the best approaches to treat PTSD. In this regard, pharmacological interventions provide a possible way to erase or lessen the fear memory of the traumatic event. The screening and identification of drugs is one of the crucial steps to introduce new potent drugs in preclinical setup. Pavlovian fear conditioning is the well known experimental protocol to study fear memory. In this article, we are presenting a detailed method of Pavlovian fear conditioning which we have optimized in our lab for the identification of drugs having the potential to disrupt fear memory in the PTSD-rat model. In this protocol, various stages of memory formation including consolidation, reconsolidation, and extinction have been targeted to study the effect of a particular drug.•The protocol provides step by step procedure to study the effects of known or putative drugs in an animal model of PTSD.•The method also explains the separate protocols to target specific stages of memory so that one can identify the effects of drugs on a particular phase of remote or recent memory formation.

Supplementation of Taurine Insulates Against Oxidative Stress, Confers Neuroprotection and Attenuates Memory Impairment in Noise Stress Exposed Male Wistar Rats.

Noise has always been an important environmental factor that induces health problems in the general population. Due to ever increasing noise pollution, humans are facing multiple auditory and non-auditory problems including neuropsychiatric disorders. In modern day life it is impossible to avoid noise due to the rapid industrialization of society. Continuous exposure to noise stress creates a disturbance in brain function which may lead to memory disorder. Therefore, it is necessary to find preventive measures to reduce the deleterious effects of noise exposure. Supplementation of taurine, a semi essential amino acid, is reported to alleviate psychiatric disorders. In this study noise-exposed (100 db; 3 h daily for 15 days) rats were supplemented with taurine at a dose of 100 mg/kg for 15 days. Spatial and recognition memory was assessed using the Morris water maze and novel object recognition task, respectively. Results of this study showed a reversal of noise-induced memory impairment in rats. The derangements of catecholaminergic and serotonergic levels in the hippocampus and altered brain antioxidant enzyme activity due to noise exposure were also restored by taurine administration. This study highlights the importance of taurine supplementation to mitigate noise-induced impaired memory via normalizing the neurochemical functions and reducing oxidative stress in rat brain.

Free L-glutamate-induced modulation in oxidative and neurochemical profile contributes to enhancement in locomotor and memory performance in male rats.

Glutamate (Glu), the key excitatory neurotransmitter in the central nervous system, is considered essential for brain functioning and has a vital role in learning and memory formation. Earlier it was considered as a harmful agent but later found to be useful for many body functions. However, studies regarding the effects of free L-Glu administration on CNS function are limited. Therefore, current experiment is aimed to monitor the neurobiological effects of free L-Glu in male rats. L-Glu was orally administered to rats for 5-weeks and changes in behavioral performance were monitored. Thereafter, brain and hippocampus were collected for oxidative and neurochemical analysis. Results showed that chronic supplementation of free L-Glu enhanced locomotor performance and cognitive function of animals which may be attributed to the improved antioxidant status and cholinergic, monoaminergic and glutamatergic neurotransmission in brain and hippocampus. Current results showed that chronic supplementation of L-Glu affects the animal behaviour and brain functioning via improving the neurochemical and redox system of brain. Free L-Glu could be a useful therapeutic agent to combat neurological disturbances however this requires further targeted studies.

Blockade of muscarinic receptors impairs reconsolidation of older fear memory by decreasing cholinergic neurotransmission: A study in rat model of PTSD.

The age and strength of fear memory are two potential parameters that can be influenced by the impairing effects of pharmacological agents on reconsolidation of fear memory. In reconsolidation, stored information is rendered labile again after being reactivated. Pharmacological manipulations at this stage result in an inability to retrieve the fear memories, suggesting that they are erased or persistently inhibited. This fear memory impairment phenomenon can be valuable to treat post-traumatic stress disorders (PTSD). Previously ß-adrenergic antagonist propranolol has been repeatedly reported to impair fear memory in the treatment of PTSD. Atropine has also shown to disrupt memory formation. The present study was therefore designed to compare the effects of atropine and propranolol on reconsolidation of older fear memory in rat model of PTSD using Pavlovian fear conditioning apparatus. For this purpose 18 rats were taken and divided into control, atropine and propranolol groups and subjected to Pavlovian fear conditioning trials in order to develop animal model of PTSD. To evaluate the reconsolidation impairment of fear memory by atropine and propranolol, short term and long term memory was tested after reactivation of fear memory in rats. The present findings demonstrate that atropine significantly decreases fear expression. These results suggest that atropine significantly reduces the strength of fear memories and may be effective in the treatment of psychiatric disorders especially in PTSD.

Amelioration of motor and non-motor deficits and increased striatal APoE levels highlight the beneficial role of pistachio supplementation in rotenone-induced rat model of PD.

Pistachio contains polyphenolic compounds including flavonoids and anthocyanins which have antioxidant and antiinflammatory activity. Present study was aimed to evaluate the protective effects of pistachio on neurobehavioral and neurochemical changes in rats with Parkinson's disease (PD). Animal model of PD was induced by the injection of rotenone (1.5 mg/kg/day, s.c.) for 8 days. Pistachio (800 mg/kg/day, p.o.) was given for two weeks in both pre- and post-treatment. At the end of treatment brain was dissected out and striatum was isolated for biochemical and neurochemical analysis. Memory was assessed by Morris water maze (MWM) and novel object recognition (NOR) test while open field test (OFT), Kondziela inverted screen test (KIST), pole test (PT), beam walking test (BWT), inclined plane test (IPT) and footprint (FP) test were used to observe motor behavior. Rotenone administration significantly (p < 0.01) impaired the memory but pistachio in both pre- and post-treatment groups significantly (p < 0.01) improved memory performance. Rotenone-induced motor deficits were significantly attenuated in both pre- and post-pistachio treatment. Increased oxidative stress and decreased DA and 5-HT levels induced by rotenone were also significantly attenuated by pistachio supplementation. Furthermore, raised apolipoprotein E (APoE) levels in rotenone injected rats were also normalized following treatment with pistachio. Present findings show that pistachio possesses neuroprotective effects and improves memory and motor deficits via increasing DA levels and improving oxidative status in brain.

Naringenin protects AlCl3/D-galactose induced neurotoxicity in rat model of AD via attenuation of acetylcholinesterase levels and inhibition of oxidative stress.

Currently prescribed medications for the treatment of Alzheimer's disease (AD) that are based on acetylcholinesterase inhibition only offer symptomatic relief but do not provide protection against neurodegeneration. There appear to be an intense need for the development of therapeutic strategies that not only improve brain functions but also prevent neurodegeneration. The oxidative stress is one of the main causative factors of AD. Various antioxidants are being investigated to prevent neurodegeneration in AD. The objective of this study was to investigate the neuroprotective effects of naringenin (NAR) against AlCl3+D-gal induced AD-like symptoms in an animal model. Rats were orally pre-treated with NAR (50 mg/kg) for two weeks and then exposed to AlCl3+D-gal (150 mg/kg + 300 mg/kg) intraperitoneally for one week to develop AD-like symptoms. The standard drug, donepezil (DPZ) was used as a stimulator of cholinergic activity. Our results showed that NAR pre-treatment significantly protected AD-like behavioral disturbances in rats. In DPZ group, rats showed improved cognitive and cholinergic functions but the neuropsychiatric functions were not completely improved and showed marked histopathological alterations. However, NAR not only prevented AlCl3+D-gal induced AD-like symptoms but also significantly prevented neuropsychiatric dysfunctions in rats. Results of present study suggest that NAR may play a role in enhancing neuroprotective and cognition functions and it can potentially be considered as a neuroprotective compound for therapeutic management of AD in the future.