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

Striatal neurons grown in low density culture on serum-free media and in th e 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 trophi c influences, such as, growth factors, neurotransmitters, antioxidants or K Cl-mediated depolarization could improve their survival. We found that stri atal 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 mu M dopamine (DA) or o ther monoamines. Although the survival effect of DA was mimicked by the spe cific D1 receptor agonist, SKF38393, no D1 or D2 receptor antagonists block ed the effect. As with DA, chronic depolarization with KCl(12-39 mM) or tre atment with antioxidants, such as the vitamin E analog, Trolox (10-10-500 m u M), or the hormone, melatonin (10-10-500 mu M) also rescued striatal neur ons from impending cell death. Surprisingly, growth Factors, such as BDNF, bFGF, GDNF, NGF, NT3 and EGF, demonstrated no ability to rescue striatal ne urons in this model, suggesting that death was not solely caused by the abs ence of essential trophic factors. We conclude that a variety of agents, bu t not growth factors, can prevent the demise of striatal neurons, presumabl y by neutralizing damage at one or more steps in the death cascade. (C) 199 9 Elsevier Science B.V. All rights reserved.