Neurotrophic and neurotoxic effects of zinc on neonatal cortical neurons.
Although zinc exerts direct neurotoxic action, this metal is also essential for the activity of numerous biological systems and zinc deficiency has been associated with various pathologies. We investigated the cellular responses and neuronal viability following exposure to different concentrations of zinc in primary cultures of neonatal rat cortical neurons. Higher concentrations of zinc (0.15 and 0.2 mM) triggered excessive zinc influx, glutathione depletion and ATP loss leading to necrotic neuronal death. In contrast, lower concentrations of zinc (0.05 and 0.1 mM) attenuated serum-deprivation induced apoptotic neuronal death. The antiapoptotic action of low amounts of zinc was found both in mixed cultures and neuron-enriched cultures indicating the independence of glial mediator. Neurotrophic action was not accompanied by significant alteration in those cellular responses but required chelatable zinc. The N-methyl-D-aspartate (NMDA) antagonist, MK-801, mimicked the beneficial effect of zinc in protecting neuronal death. Moreover, both MK-801 and zinc eliminated NMDA-induced neuronal injury. The results suggest that zinc is an intrinsic factor for neuron survival and exogenous zinc, in low amounts, is an active neuroprotectant against serum deprivation in part through the antagonism of NMDA receptor activation.
Chen
Chun-Jung
CJ
Department of Education and Research, Taichung Veterans General Hospital, No. 160, Section 3, Taichung-Gang Road, Taichung 407, Taiwan, ROC. cjchen@vghtc.gov.tw
Liao
Su-Lan
SL
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D004587:Electrophoresis, Agar Gel; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000633:toxicity*
D005978:Glutathione; D015032:Zinc