Neurotransmitters, KCl and antioxidants rescue striatal neurons from apoptotic cell death in culture

• Published in: Brain research 1999-01, Vol.816 (2), p.276-285
• Main Authors: Iacovitti, Lorraine, Stull, Natalie D, Mishizen, Amanda
• Format: Article
• Language: English
• Subjects: Ageing, cell death; Animals; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cell physiology; Cell Survival - drug effects; Cells, Cultured; Corpus Striatum - drug effects; Corpus Striatum - pathology; Culture Media, Serum-Free; Dopamine Agonists - pharmacology; Fundamental and applied biological sciences. Psychology; Growth factor; Membrane Potentials - drug effects; Mice; Molecular and cellular biology; Neurons - drug effects; Neurons - pathology; Neurotransmitter; Neurotransmitter Agents - pharmacology; Potassium Chloride - pharmacology; Striatum; Tissue culture
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(98)00955-X

Striatal neurons grown in low density culture on serum-free media and in the absence of glia die within 3 days of plating. In this study, we sought to determine the mechanism of cell death (e.g., apoptosis) and whether trophic influences, such as, growth factors, neurotransmitters, antioxidants or KCl-mediated depolarization could improve their survival. We found that striatal neurons grown in this manner die via apoptosis unless treated with one of several different rescuing agents. One way to prevent the death of most striatal neurons was continual treatment with 5–20 μM dopamine (DA) or other monoamines. Although the survival effect of DA was mimicked by the specific D1 receptor agonist, SKF38393, no D1 or D2 receptor antagonists blocked the effect. As with DA, chronic depolarization with KCl (12–39 mM) or treatment with antioxidants, such as the vitamin E analog, Trolox (10–10–500 μM), or the hormone, melatonin (10–10–500 μM) also rescued striatal neurons from impending cell death. Surprisingly, growth factors, such as BDNF, bFGF, GDNF, NGF, NT3 and EGF, demonstrated no ability to rescue striatal neurons in this model, suggesting that death was not solely caused by the absence of essential trophic factors. We conclude that a variety of agents, but not growth factors, can prevent the demise of striatal neurons, presumably by neutralizing damage at one or more steps in the death cascade.