Modulation of brain glutamate dehydrogenase as a tool for controlling seizures
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 effe...
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2015-12-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.1515/acph-2015-0033 |
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| author | Rasgado Lourdes A. Vega Reyes Guillermo Ceballos Díaz Fernando Vega |
| author_facet | Rasgado Lourdes A. Vega Reyes Guillermo Ceballos Díaz Fernando Vega |
| author_sort | Rasgado Lourdes A. Vega |
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| description | 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 aketoglutarate (αK) 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 αK caused by the chemoconvulsant pentylenetetrazol. These results suggest that AEDs act by modulating brain GDH activity, which in turn decreased 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. |
| format | Article |
| id | doaj-art-6268dba2f1a245b6aa55d51527e966d2 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2015-12-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-6268dba2f1a245b6aa55d51527e966d22025-02-02T17:47:12ZengSciendoActa Pharmaceutica1846-95582015-12-0165444345210.1515/acph-2015-0033acph-2015-0033Modulation of brain glutamate dehydrogenase as a tool for controlling seizuresRasgado Lourdes A. Vega0Reyes Guillermo Ceballos1Díaz Fernando Vega2Laboratorio 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. MéxicoLaboratorio 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., MéxicoLaboratorio 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. MéxicoGlutamate (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 aketoglutarate (αK) 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 αK caused by the chemoconvulsant pentylenetetrazol. These results suggest that AEDs act by modulating brain GDH activity, which in turn decreased 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.https://doi.org/10.1515/acph-2015-0033gdhantiepilepticsoxygen consumptiongabaglutamate |
| spellingShingle | Rasgado Lourdes A. Vega Reyes Guillermo Ceballos Díaz Fernando Vega Modulation of brain glutamate dehydrogenase as a tool for controlling seizures Acta Pharmaceutica gdh antiepileptics oxygen consumption gaba glutamate |
| title | Modulation of brain glutamate dehydrogenase as a tool for controlling seizures |
| title_full | Modulation of brain glutamate dehydrogenase as a tool for controlling seizures |
| title_fullStr | Modulation of brain glutamate dehydrogenase as a tool for controlling seizures |
| title_full_unstemmed | Modulation of brain glutamate dehydrogenase as a tool for controlling seizures |
| title_short | Modulation of brain glutamate dehydrogenase as a tool for controlling seizures |
| title_sort | modulation of brain glutamate dehydrogenase as a tool for controlling seizures |
| topic | gdh antiepileptics oxygen consumption gaba glutamate |
| url | https://doi.org/10.1515/acph-2015-0033 |
| work_keys_str_mv | AT rasgadolourdesavega modulationofbrainglutamatedehydrogenaseasatoolforcontrollingseizures AT reyesguillermoceballos modulationofbrainglutamatedehydrogenaseasatoolforcontrollingseizures AT diazfernandovega modulationofbrainglutamatedehydrogenaseasatoolforcontrollingseizures |