Activation of GABA(A) receptors by taurine and muscimol blocks the neurotoxicity of beta-amyloid in rat hippocampal and cortical neurons

Paula-Lima, AC; De Felice, FG; Brito-Moreira, J; Ferreira, ST


The beta-amyloid peptide (A beta) is centrally related to the pathogenesis of Alzheimer's disease (AD) and is potently neurotoxic to central nervous system neurons. The neurotoxicity of A beta has been partially related to the over activation of glutamatergic transmission and excitotoxicity. Taurine is a naturally occurring beta-amino acid present in the mammalian brain. Due to its safety and tolerability, taurine has been clinically used in humans in the treatment of a number of non-neurological disorders. Here, we show that micromolar doses of taurine block the neurotoxicity of A beta to rat hippocampal and cortical neurons in culture. Moreover, taurine also rescues central neurons from the excitotoxicity induced by high concentrations of extracellular glutamate. Neuroprotection by taurine is abrogated by picrotoxin, a GABA(A) receptor antagonist. GABA and muscimol, an agonist of the GABA(A) receptor, also block neuronal death induced by A beta in rat hippocampal and cortical neurons. These results suggest that activation of GABA(A) receptors protects neurons against A beta toxicity in AD-affected regions of the mammalian brain and that taurine should be investigated as a novel therapeutic tool in the treatment of AD and of other neurological disorders in which excitotoxicity plays a relevant role. (c) 2005 Elsevier Ltd. All rights reserved.

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Título según WOS: ID WOS:000233695400005 Not found in local WOS DB
Título de la Revista: NEUROPHARMACOLOGY
Volumen: 49
Número: 8
Fecha de publicación: 2005
Página de inicio: 1140
Página final: 1148


Notas: ISI