Decreased glutamate receptor binding and NMDA R1 gene expression in hippocampus of pilocarpine-induced epileptic rats: neuroprotective role of Bacopa monnieri extract.
The potential for antiepileptic drugs to negatively impact cognitive abilities has generated renewed interest in herbal drugs and formulations in the treatment of epilepsy. Bacopa monnieri is one such widely used revitalizing herb that purportedly strengthens nervous function and also possesses memory-enhancing, antioxidative, antiepileptic, and anti-inflammatory properties. We investigated the neuroprotective role of B. monnieri extract in alteration of glutamate receptor binding and gene expression of NMDA R1 in hippocampus of temporal lobe epileptic rats. In association with pilocarpine-induced epilepsy, there was significant downregulation of NMDA R1 gene expression and glutamate receptor binding without any change in its affinity. B. monnieri treatment of epileptic rats significantly reversed the expression of NMDA R1 and glutamate receptor binding alterations to near-control levels. Also, in the epileptic rats, we measured a significant increase in the activity of glutamate dehydrogenase, which neared the control level after B. monnieri treatment. The therapeutic effect of B. monnieri was also observed in the Morris water maze experiment. These data together indicate the neuroprotective role of B. monnieri extract in glutamate-mediated excitotoxicity during seizures and cognitive damage occurring in association with pilocarpine-induced epilepsy.
Khan
Reas
R
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682 022, Kerala, India.
Krishnakumar
Amee
A
Paulose
C S
CS
D000704:Analysis of Variance; D000818:Animals; D034681:Bacopa / Q000737:chemistry*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008517:Phytotherapy / Q000379:methods*; D010862:Pilocarpine; D028321:Plant Preparations / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
D005969:Glutamate Dehydrogenase; D018698:Glutamic Acid; D010862:Pilocarpine; D028321:Plant Preparations; D016194:Receptors, N-Methyl-D-Aspartate