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Acta Pharmaceutica, Vol. 65 No. 4, 2015.

Original scientific paper

https://doi.org/10.1515/acph-2015-0033

Modulation of brain glutamate dehydrogenase as a tool for controlling seizures

LOURDES A. VEGA RASGADO ; Laboratorio de Neuroquímica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala S/N, Colonia Casco de Santo Tomás, C.P. 11340, México, D.F., México
GUILLERMO CEBALLOS REYES FERNANDO VEGA DÍAZ ; Laboratorio de Investigación Integral Cardiometabólica, Sección de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional Plan de San Luis y Díaz Mirón, Colonia Casco de Santo Tomás, C.P. 11340, México D.F., México

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Abstract

Glutamate (Glu) is a major excitatory neurotransmitter involved in epilepsy. Glu is synthesized by glutamate dehydrogenase (GDH, E.C. 1.4.1.3) and dysfunction of the enzymatic activity of GDH is associated with brain pathologies. The main goal of this work is to establish the role of GDH in the effects of antiepileptic drugs (AEDs) such as valproate (VALP), diazepam (DIAZ) and diphenylhydantoin (DPH) and its repercussions on oxygen consumption. Oxidative deamination of Glu and reductive amination of α-ketoglutarate (K) in mice brain were investigated. Our results show that AEDs decrease GDH activity and oxygen consumption in vitro. In ex vivo experiments, AEDs increased GDH activity but decreased oxygen consumption during Glu oxidative deamination. VALP and DPH reversed the increase in reductive amination of K caused by the chemoconvulsant pentylenetetrazol. These results suggest that AEDs act by modulating brain GDH activity, which in turn decreases oxygen consumption. GDH represents an important regulation point of neuronal excitability, and modulation of its activity represents a potential target for metabolic treatment of epilepsy and for the development of new AEDs.

Keywords

GDH; antiepileptics; oxygen consumption; GABA; glutamate

Hrčak ID:

142805

URI

https://hrcak.srce.hr/142805

Publication date:

31.12.2015.

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