Withania somnifera against glutamate excitotoxicity and neuronal cell loss in a scopolamine-induced rat model of Alzheimer’s disease

Alzheimer’s disease, a chronic and progressive neurodegenerative disorder with no prevention and cure, affecting nearly 50 million people worldwide. Glutamate is the principal excitatory neurotransmitter in the central nervous system involved in 50% of basic brain functions, especially cortical and hippocampal regions, like memory, cognition, and learning. The glutamate-mediated toxicity is termed as excitotoxicity. The present study was aimed to determine whether the methanolic and water extracts of root from the medicinal plant, Withania somnifera, could decrease the glutamate excitotoxicity and its related neuronal cell loss in a scopolamine-induced animal model of Alzheimer's disease. The rats were randomly divided into different groups of 5 in each: normal control - treated orally with saline; AD model - injected intra peritoneally with scopolamine (2 mg/Kg body wt) alone to induce Alzheimer's disease; AD model rats treated orally with the methanolic extract (AD+ME-WS) (300 mg/Kg body wt), water extract (AD+WE-WS) (300 mg/Kg body wt), and donepezil hydrochloride, a standard control (AD+DZ) (5 mg/Kg body wt) for 30 consecutive days. Increased glutamate (Glu) levels and decreased glutamate dehydrogenase (GDH) activity were reversed with Withania somnifera root extracts in both the cerebral cortex and hippocampus regions in scopolamine-induced Alzheimer's disease model rat brain. The histopathological studies of the same treatment also showed protection against neuronal cell loss in both regions. These results support the idea that these extracts could be effective for the reduction of brain damage by preventing glutamate excitotoxicity generated neuronal cell loss in the scopolamine-induced Alzheimer's disease model. DOI: http://dx.doi.org/10.5281/zenodo.442677

Withania somnifera against glutamate excitotoxicity and neuronal cell loss in a scopolamine-induced rat model of Alzheimer’s disease

Alzheimer’s disease, a chronic and progressive neurodegenerative disorder with no prevention and cure, affecting nearly 50 million people worldwide. Glutamate is the principal excitatory neurotransmitter in the central nervous system involved in 50% of basic brain functions, especially cortical and hippocampal regions, like memory, cognition, and learning. The glutamate-mediated toxicity is termed as excitotoxicity. The present study was aimed to determine whether the methanolic and water extracts of root from the medicinal plant, Withania somnifera, could decrease the glutamate excitotoxicity and its related neuronal cell loss in a scopolamine-induced animal model of Alzheimer's disease. The rats were randomly divided into different groups of 5 in each: normal control - treated orally with saline; AD model - injected intra peritoneally with scopolamine (2 mg/Kg body wt) alone to induce Alzheimer's disease; AD model rats treated orally with the methanolic extract (AD+ME-WS) (300 mg/Kg body wt), water extract (AD+WE-WS) (300 mg/Kg body wt), and donepezil hydrochloride, a standard control (AD+DZ) (5 mg/Kg body wt) for 30 consecutive days. Increased glutamate (Glu) levels and decreased glutamate dehydrogenase (GDH) activity were reversed with Withania somnifera root extracts in both the cerebral cortex and hippocampus regions in scopolamine-induced Alzheimer's disease model rat brain. The histopathological studies of the same treatment also showed protection against neuronal cell loss in both regions. These results support the idea that these extracts could be effective for the reduction of brain damage by preventing glutamate excitotoxicity generated neuronal cell loss in the scopolamine-induced Alzheimer's disease model. DOI: http://dx.doi.org/10.5281/zenodo.442677

EVALUATION OF ROTENONE INDUCED PARKINSON'S DISEASE ON GLUTAMATE METABOLISM AND PROTECTIVE STRATEGIES OF BACOPA MONNIERI

ABSTRACT: Bacopa monnieri (BM; Family: Scrophulariaceae), also referred as Brahmi has been used for centuries in Ayurvedic system of medicine as a brain tonic, memory enhancer, revitaliser of sensory organs, antianxiety, cardio-tonic, diuretic, antidepressant and anticonvulsant agent, and the pharmacological actions are mainly attributed to the saponin compounds present in the alcoholic extract of the plant. The present study was carried out with a specific aim to examine the neuroprotective effect of Rotenone (RT) induced Parkinson's disease (PD) with particular reference to glutamate metabolism in different regions of rat brain. The rats were divided into four groups of six in each, group 1 received Saline water, group 2 received RT through i.p. route for 60 days to induce PD. The BM extract was given orally 20 days before induction of the PD to group 3 and group 4 received Levodopa (LD) orally, referred as drug control. The levels of Glutamine content, Glutamate dehydrogenase (GDH), Glutamine synthetase (GS) and Glutaminase were measured. Glutamine content and activity levels of GDH, GS were significantly depleted and elevated Glutaminase activity was found in different brain regions of rat during RT induced PD when compared to control rats. Treatment with BM and LD caused significant elevation in Glutamine content and the activity levels of GDH, GS and depletion in glutaminase activity in different brain regions of rats when compared to induced PD rats. Our results suggest the ability of BM extract to modulate glutamate metabolism in different brain regions of induced rodent model of PD