Down-regulation of cerebellar 5-HT(2C) receptors in pilocarpine-induced epilepsy in rats: therapeutic role of Bacopa monnieri extract

J Neurol Sci. 2009 Sep 15;284(1-2):124-8. doi: 10.1016/j.jns.2009.04.032. Epub 2009 May 13.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / isolation & purification
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Ataxia / drug therapy
  • Ataxia / etiology
  • Bacopa / chemistry*
  • Carbamazepine / pharmacology
  • Carbamazepine / therapeutic use
  • Cerebellum / drug effects
  • Cerebellum / metabolism*
  • Down-Regulation / drug effects
  • Drug Evaluation, Preclinical
  • Epilepsy / chemically induced
  • Epilepsy / drug therapy*
  • Epilepsy / genetics
  • Epilepsy / metabolism
  • Male
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Phytotherapy*
  • Pilocarpine / toxicity
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Protein Binding / drug effects
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2C / genetics
  • Receptor, Serotonin, 5-HT2C / metabolism*
  • Serotonin / metabolism*
  • Serotonin Receptor Agonists / isolation & purification
  • Serotonin Receptor Agonists / pharmacology
  • Serotonin Receptor Agonists / therapeutic use*

Substances

  • Anticonvulsants
  • Neuroprotective Agents
  • Plant Extracts
  • Receptor, Serotonin, 5-HT2C
  • Serotonin Receptor Agonists
  • Pilocarpine
  • Serotonin
  • Carbamazepine