Ethanol neurotoxicity on neuroblast-enriched cultures from three-day-old chick embryo is attenuated by the neuronotrophic action of GABA |
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| Institution: | 1. The Wellcome Trust/Cancer Research UK Gurdon Institute & Department of Biochemistry, University of Cambridge, Cambridge, UK;2. UCL Great Ormond Street Institute of Child Health, Zayed Centre for Research into Rare Disease in Children, University College London, 20 Guilford Street, London WC1N 1DZ, UK;1. Department of Neurology, Huashan Hospital, Shanghai, 200040, China;2. Department of Neurology, National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200433, China;3. Stem Cell Core Facility, Stem Cells Australia, The University of Melbourne, Victoria, 3010, Australia;4. Illawarra Health and Medical Research Institute, University of Wollongong, NSW, 2522 Australia;5. School of Medicine, University of Tasmania, Hobart, Tasmania, 7001, Australia;6. Department of Neuroscience, Central Clinical School, Monash University, The Alfred Centre, VIC 3004, Australia |
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| Abstract: | In the present study, using neuroblast-enriched cultures derived from three-day-old chick embryos (E3WE), we examined the morphological effects of ethanol and/or GABA, as well as the developmental profile of the cholinergic and GABAergic neuronal phenotypes, as assessed by the activities of choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD). Cultures exposed to ethanol (50 mM) exhibited smaller and fewer aggregates than controls with a neuritic network that lacked fasciculation. In cultures treated with GABA (10?5 M) alone or ethanol + GABA the size and number of the neuronal aggregates was increased and also neuritic arborization and fasciculation was enhanced. Thus, addition of GABA restored the normal growth pattern in the ethanol-treated cultures. As previously shown, E3WE culture treated with ethanol alone showed a decrease in both ChAT and GAD activities compared to controls. Both cholinergic and GABAergic neuronal phenotypes were enhanced in cultures treated with GABA as assessed by increases in ChAT and GAD activities, respectively, compared to controls. Moreover, in cultures treated concomitantly with ethanol and GABA both ChAT and GAD activities were higher than in ethanol-alone-treated cultures. Thus, the presence of GABA in the ethanol-treated cultures counteracted the decline in ChAT and GAD activities observed in the ethanol-alone-treated cultures. We concluded that GABA through its neuronotrophic actions can rescue neuroblasts from ethanol insult and restore neuronal phenotypes. |
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