Topiramate modulates hippocampus NMDA receptors via brain Ca²⁺ homeostasis in pentylentetrazol-induced epilepsy of rats

Abstract

Background: Increase in neuronal Ca²⁺, activation of hippocampus N-methyl-D-aspartate receptor (NMDAR) and defects in enzymes such as brain cortex microsomal membrane Ca²⁺-ATPase (MMCA) are thought to play a role in epilepsy. Topiramate (TOP) is a novel drug with broad antiepileptic effect, and its effect on brain cortex MMCA is not known. We investigated effects of TOP on pentylentetrazol (PTZ)-induced MMCA activity and NMDAR subunits in rat brain.

Materials and methods: Thirty-two rats were randomly divided into four equal groups. The first group and second groups were used for the control and PTZ groups, respectively. 50 and 100 mg TOP were administered to rats constituting the third (TOP50) and fourth (TOP100) groups for 7 days, respectively. At the end of 7 days, all groups except the first received a single dose PTZ. Brain and hippocampus samples were taken at 3 hrs after PTZ administration.

Results: The microsomal MMCA activity was lower in the PTZ group than in control although the MMCA activities were higher in the treatment group than in PTZ group. Brain cortex total calcium levels, the hippocampus NMDAR 2A and 2B subunit concentrations were higher in the PTZ group than in control although their concentrations were decreased by TOP50 and TOP100 administration. Total brain cortex calcium and hippocampus NMDAR 2A and 2B subunit concentrations were higher in TOP100 group than in TOP50 group.

Conclusion: The two doses of TOP modulated MMCA activity, total brain cortex calcium and hippocampus NMDAR 2A and 2B subunit concentrations in the epileptic rats.

Keywords::

• Topiramate
• Ca²⁺ signaling
• hippocampus
• brain
• NMDA receptors

Acknowledgement

The report N.Y and M.Y. formulated the present hypothesis and were responsible for writing the report. N.G. and M.Y. were responsible for the data analyses. S.K., V.A.Y. and H.V. made critical revisions to the manuscript. The study was supported by the Scientific Research Project Unit of Suleyman Demirel University (BAP-1462-TU-06).

Declaration of interest

The authors declared no conflict interest.