Down-regulation of cerebellar 5-HT(2C) receptors in pilocarpine-induced epilepsy in rats: therapeutic role of Bacopa monnieri extract.
Epilepsy is a syndrome of episodic brain dysfunction characterized by recurrent unpredictable, spontaneous seizures. Cerebellar dysfunction is a recognized complication of temporal lobe epilepsy and it is associated with seizure generation, motor deficits and memory impairment. Serotonin is known to exert a modulatory action on cerebellar function through 5HT(2C) receptors. 5-HT(2C) receptors are novel targets for developing anti-convulsant drugs. In the present study, we investigated the changes in the 5-HT(2C) receptors binding and gene expression in the cerebellum of control, epileptic and Bacopa monnieri treated epileptic rats. There was a significant down regulation of the 5-HT content (p<0.001), 5-HT(2C) gene expression (p<0.001) and 5-HT(2C) receptor binding (p<0.001) with an increased affinity (p<0.001). Carbamazepine and B. monnieri treatments to epileptic rats reversed the down regulated 5-HT content (p<0.01), 5-HT(2C) receptor binding (p<0.001) and gene expression (p<0.01) to near control level. Also, the Rotarod test confirms the motor dysfunction and recovery by B. monnieri treatment. These data suggest the neuroprotective role of B. monnieri through the upregulation of 5-HT(2C) receptor in epileptic rats. This has clinical significance in the management of epilepsy.
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682 022, Kerala, India.
Amee
A
Krishnakumar
Pretty Mary
PM
Abraham
Jes
J
Paul
C S
CS
Paulose
D000818:Animals; D000927:Anticonvulsants / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D001259:Ataxia / Q000188:drug therapy / Q000209:etiology; D034681:Bacopa / Q000737:chemistry*; D002220:Carbamazepine / Q000494:pharmacology / Q000627:therapeutic use; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010862:Pilocarpine / Q000633:toxicity; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*
D000927:Anticonvulsants; D018696:Neuroprotective Agents; D010936:Plant Extracts; D044405:Receptor, Serotonin, 5-HT2C; D017366:Serotonin Receptor Agonists; D010862:Pilocarpine; D012701:Serotonin; D002220:Carbamazepine