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.
Krishnakumar
Amee
A
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682 022, Kerala, India.
Abraham
Pretty Mary
PM
Paul
Jes
J
Paulose
C S
CS
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