Neurotoxicity Research

, Volume 5, Issue 5, pp 323–327 | Cite as

Neuroprotection against Aβ and glutamate toxicity by melatonin: Are GABA receptors involved?

  • Andréa C. Paula Lima
  • Paulo Roberto Louzada
  • Fernando G. De Mello
  • Sérgio T. Ferreira


The β-amyloid peptide (Aβ) is centrally related to the pathogenesis of Alzheimer's disease (AD). Previous studies have suggested that the neurotoxicity of Aβ may be related to the over activation of glutamatergic transmission and excitotoxicity, and that blockade of glutamate receptors prevents Aβ-induced cell death. Here, we show that melatonin, a pineal hormone, protects chick retinal neurons in culture against the neurotoxicity of Aβ and glutamate. Right-angle light scattering and thioflavin T fluorescence measurements, as well as light microscopy analysis, indicated that, under our experimental conditions, melatonin had no effect on the aggregation of Aβ. Interestingly, the neuroprotective action of melatonin against the toxicity of Aβ was significantly decreased in the presence of picrotoxin, an antagonist of GABAA-like receptors. By itself, picrotoxin had no effect. These results suggest that the neuroprotective effects of melatonin against Aβ neurotoxicity could be at least in part related to a decrease in the excitatory tonus, mediated by activation of GABA receptors and the resulting hyperpolarization of the neurons. Thus, selective pharmacological manipulation of neuronal excitatory/inhibitory tonus could be a potentially interesting new approach in the treatment of AD.

Key words

Melatonin GABA Amyloid Glutamate Neuroprotection 


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Copyright information

© FP Graham Publishing Co 2003

Authors and Affiliations

  • Andréa C. Paula Lima
    • 1
  • Paulo Roberto Louzada
    • 1
  • Fernando G. De Mello
    • 2
  • Sérgio T. Ferreira
    • 1
  1. 1.Departamento de Bioquimica Médica, Instituto de Ciências BiomédicasUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  2. 2.Instituto de Biofisica Carlos Chagas FilhoUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil

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