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.

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.

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.

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.

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.

Spirulina platensis (Blue-green algae): A miracle from sea combats the oxidative stress and improves behavioral deficits in an animal model of Schizophrenia.

Spirulina platensis (blue-green algae) is a nutritional supplement. It constitutes of high content of protein, antioxidants, various phytopigments and possesses neuroprotective activities. Schizophrenia (SZ) is recognized as a neuropsychiatric disorder in humans with a reduced lifespan followed with impairments in social as well as vocational functioning. Major psychotic symptoms of SZ cluster into three categories: positive, negative and cognitive dysfunctions. Dizocilpine recognized as one of the best drugs to mimic full spectrum of SZ can develop an animal model of the disorder. Various antipsychotics are considered as approved treatment therapy for the psychotic symptoms of SZ but they also exert adverse effects. Thus, there is an excessive need for novel treatment(s) with negligible adverse effects. Present study was designed to evaluate the neuroprotective effects of spirulina in ameliorating the psychosis- like symptoms in dizocilpine-induced rat model of SZ. Spirulina was tested at the dose of 180 mg/kg. Results showed that administration of spirulina improved behavioral deficits and combated the oxidative damage evident by a significant reduction in lipid peroxidation and increase in antioxidant level. Thus, from present findings it may be suggested that spirulina can be used as a therapy for preventive or therapeutic measures.

Acute aluminum chloride toxicity revisited: Study on DNA damage and histopathological, biochemical and neurochemical alterations in rat brain.

AIMS: Due to rapid increase in industrialization in the last few years, use of aluminum (Al) and its alloys have been increased in different industrial fields. Ample evidence supports the neurotoxic effects of chronic aluminum chloride (AlCl3) administration in rats but acute Al toxicity has been less described so the present study was aimed to investigate the neurotoxic effects of acute AlCl3. MAIN METHODS: To investigate such effects 12 male albino Wistar rats were randomly divided into control and test rats. AlCl3 at a dose of 150 mg/kg was intraperitoneally injected to test rats for 7 days. Rats were subjected to behavioral assessments 24 h after last dose and after behavioral assessment rats were sacrificed to collect brain samples for further neurochemical, biochemical and histopathological examinations. KEY FINDINGS: In the present study acute administration of AlCl3 resulted in noticeable behavioral deficits. Cognitive deficits and neuropsychiatric disturbances were evident in AlCl3 injected rats. Test rats also exhibited marked antioxidant enzymes, cholinergic, serotonergic and dopaminergic dysfunctions and DNA fragmentation. Histopathological alterations were observed in hippocampus and cortex of rats injected with AlCl3. SIGNIFICANCE: The observed effects may be due to pro-oxidant nature of Al and its participation in free radical mediated cellular injury. Al by promoting oxidative stress, impairing antioxidant defense system and altering brain neurochemistry may act as a potent neurotoxic agent as evident from observed histopathological alterations in brain of test rats. This investigation may further confirm and shed some more light on deleterious effects of acute Al intoxication on brain.

Quantitative and qualitative assessment of additives present in broiler chicken feed and meat and their implications for human health.

OBJECTIVE: To determine the various constituents of commercial, broiler chicken feed and the presence of these constituents in their meat. METHODS: The experimental study was conducted at the Pakistan Council of Scientific and Industrial Research laboratory, Karachi. Samples of commercial broiler chicken feed and meat were collected in 2015 from a large poultry farm that supplies chicken meat to various suburban areas of the city. Another set of organic chickens were bred in an animal house. The samples of feed, meat and droppings were then analysed for the estimation of basic constituents and additives in the laboratory. Data was analysed using SPSS 20.0. RESULTS: The constituents were measured in 26 samples of chicken meat from each group. Calories (p<0.01), amount of protein (p<0.01), total fats (p<0.05), cholesterol (p<0.01), saturated fats (p<0.01), monounsaturated (p<0.05) and polyunsaturated fats (p<0.01) were significantly increased in commercial broiler chicken compared to that of organic chicken meat. The commercial chicken feed was found to contain crude carbohydrate, crude protein, crude fat, crude fibre, vitamins, amino acids, premixes of vitamins and toxicities of roxarsone, melamine and pesticides. Additive constituents were also present in the commercial chicken meat. These components were absent in organic chicken meat and droppings which suggests that they were absent in their feeding contents. CONCLUSIONS: Organic chickens were found to be safer for consumption than commercial chickens.

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 50mg/kg, 200mg/kg and 50mg/kg respectively for 16days. 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 (1h after training), retention (24h after training), memory extinction (4days after training), and reconsolidation (8 and 12days 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.

Dizocilpine induced psychosis-like behavior in rats: A possible animal model with full spectrum of schizophrenia.

Schizophrenia (SZ) is categorized as neuropsychiatric disorder with reduced lifespan and significant impairments in social and vocational functioning. One of the best proposed pharmacological animal models is dizocilpine, as it can mimic the full spectrum of schizophrenic disorder including positive and negative symptoms along with cognitive deficits. Dizocilpine is N-methyl-D-aspartate (NMDA) receptor antagonist known to induce hyper-locomotion and stereotyped behavior in rodents. Present study was designed to develop an animal model of SZ via intraperitoneal administration of dizocilpine in rats (100-150g) at a dose of 0.3 mg/kg for eight days. For the evaluation of positive symptoms, hyperlocomotor behavior was monitored. Negative symptoms were assessed by sucrose preference test (SPT) and social interaction test (SIT). Moreover, Cognitive deficits were evaluated by novel object recognition test (NORT). After behavioral assessments animals were decapitated for further evaluation of biochemical and neurochemical estimations. Present findings revealed that dizocilpine injected rats exhibited significant hyperlocomotor behavior, depressive symptoms and cognitive deficits. Results are further strengthened with a marked increase in lipid per oxidation (LPO) in brain and a decline in reduced glutathione (GSH) levels. Biogenic amine levels (Dopamine, DA; 5-hydroxytryptamine, 5-HT) were also significantly increased and decreased respectively. Thus, present findings suggest that dizocilpine can be used as one of the best drug to develop psychosis-like symptoms in rats and to develop an animal model following a short-term study.

Development of AD like symptoms following co-administration of AlCl3 and D-gal in rats: A neurochemical, biochemical and behavioural study.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with neurochemical and neurobehavioural alterations. Aluminium (Al) is considered as a contributing factor in the etiology of several neurodegenerative disorders like AD. D-galactose (D-gal) is a physiological nutrient but over supply induces some neurochemical and biochemical changes that exacerbate natural aging process. In this study, we aimed to develop AD animal model by co-administration of Al and D-gal in rats. Male albino Wistar rats were intraperitoneally injected with AlCl3 and D-gal at a dose of 150mg/kg and 300mg/kg respectively for one week. After one week rats were subjected to behavioural analysis. After behavioural analysis rats were decapitated to remove their brain. Biochemical and neurochemical analysis were conducted in whole brain. AlCl3+D-gal significantly induced depressive and anxious behaviour in rats. Rats cognitive abilities were also significantly impaired following AlCl3 and D-gal co-administration. AlCl3+D-gal significantly altered antioxidant enzyme activities and biogenic amine levels in whole brain. A marked increase in brain lipid peroxidation and acetylcholinesterase activity was found in test rats. These findings suggest that co-administration of AlCl3 and D-gal for one week could induce AD like symptoms and may be used to develop AD animal model.

Assessment of gait dynamics in rotenone-induced rat model of Parkinson's disease by footprint method.

Rotenone (organic pesticide and inhibitor of mitochondrial complex I) is used to generate an experimental model of Parkinson's disease (PD). In the present study, we investigated rotenone-induced locomotor deficits, gait dynamics and muscular weakness in rats. The study also determined dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels following rotenone administration. In the study, adult male rats were administered subcutaneously (s.c.) with rotenone (1.5 mg/kg/day) for 8 days. Motor activities were monitored by the Kondziela's inverted screen test, beam walking test and footprint test. Animals were decapitated after behavioral analysis and brains were dissected out for neurochemical estimation. Results showed that the levels of DA and DOPAC were significantly decreased, which further supported by significant impaired motor coordination in rotenone treated rats. In conclusion, the behavioral and neurochemical findings of our study further strengthen the previous report and emphasizes on short term administration of rotenone producing PD-like symptoms in rats.

Impact of oral supplementation of Glutamate and GABA on memory performance and neurochemical profile in hippocampus of rats.

Glutamate (GLU) and gamma-amino butyric acid (GABA) are essential amino acids (AA) for brain function serving as excitatory and inhibitory neurotransmitter respectively. Their tablets are available in market for improving gut function and muscle performance. Despite of having a major role during memory formation and processing, effects of these tablets on brain functioning like learning and memory have not been investigated. Therefore, present study is aimed to investigate the effects of orally supplemented GLU and GABA on learning and memory performance and further to monitor related effects of these orally supplemented GLU and GABA on brain levels of these AA. Three groups of rats were supplemented orally with drinking water (control group) or suspension of tablets of GABA and Glutamate, respectively for four weeks. Cognitive performance was determined using behavioral tests (Novel object recognition test, Morris water maze, Passive avoidance test) measuring recognition, spatial reference and aversive memory. Levels of GLU, GABA and acetylcholine (ACh) were estimated in rat hippocampus. Results showed that chronic oral administration of GLU and GABA tablets has a significant impact on brain function and can alter GLU and GABA content in rat hippocampus. Compared to GABA, GLU supplementation specifically enhances memory performance via increasing ACh. Thus, GLU can be suggested as a useful supplement for improving learning and memory performance and neurochemical status of brain and in future could be effective in the treatment of neurological disorders affecting learning and memory performance.

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.