Activation of GABAA receptors by taurine and muscimol blocks the neurotoxicity of β-amyloid in rat hippocampal and cortical neurons

The β-amyloid peptide (Aβ) is centrally related to the pathogenesis of Alzheimer's disease (AD) and is potently neurotoxic to central nervous system neurons. The neurotoxicity of Aβ has been partially related to the over activation of glutamatergic transmission and excitotoxicity. Taurine is a naturally occurring β-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 Aβ 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 GABAA receptor antagonist. GABA and muscimol, an agonist of the GABAA receptor, also block neuronal death induced by Aβ in rat hippocampal and cortical neurons. These results suggest that activation of GABAA receptors protects neurons against Aβ 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.