Neuroprotective role of Bacopa monnieri extract in epilepsy and effect of glucose supplementation during hypoxia: glutamate receptor gene expression.
The experiments were designed to study the glutamate gene expression during epilepsy in adult and hypoxic insult to brain during the neonatal period and the therapeutic role of neuroprotective supplements. We investigated the role of metabotropic glutamate-8 receptor (mGluR8) gene expression in cerebellum during epilepsy and neuroprotective role of Bacopa monnieri extract in epilepsy. We also studied the effect of NMDA receptor 1 (NMDAR1) gene expression during neonatal hypoxia and therapeutic role of glucose, oxygen and epinephrine supplementation. During epilepsy a significant down-regulation (P < 0.01) of mGluR8 gene expression was observed which was up-regulated (P < 0.05) near control level after B. monnieri treatment which is supported by Morris water maze experiment. In hypoxic neonates we observed up-regulation (P < 0.001) of the NMDAR1 gene expression whereas glucose and glucose + oxygen was able to significantly reverse (P < 0.001) the gene expression to near control level when compared to hypoxia and epinephrine treatment which was supported by open field test. Our results showed that B. monnieri treatment to epileptic rats significantly brought the reversal of the down-regulated mgluR8 gene expression toward control level. In neonatal rats, hypoxia induced expressional and functional changes in the NMDAR1 receptors of neuronal cells which is corrected by supplementation of glucose alone or glucose followed by oxygen during the resuscitation to prevent the glutamate related neuronal damage. Thus, the results suggest the clinical significance of corrective measures for epileptic and hypoxic management.
Paulose
C S
CS
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala, 682022, India. cspaulose@cusat.ac.in
Chathu
Finla
F
Khan
S Reas
SR
Krishnakumar
Amee
A
D000322:Adrenergic Agonists / Q000494:pharmacology; D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D034681:Bacopa / Q000737:chemistry*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004837:Epinephrine / Q000494:pharmacology; D005786:Gene Expression Regulation; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism
D000322:Adrenergic Agonists; D004837:Epinephrine; D005947:Glucose; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C111435:metabotropic glutamate receptor 8