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 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 microM 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 microM), or the hormone, melatonin (10-10-500 microM) 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.
Iacovitti
L
L
Department of Neurobiology and Anatomy, Medical College of Pennsylvania and Hahnemann University, 3200 Henry Avenue, Philadelphia, PA 19129, USA. iacovittil@auhs.edu
Stull
N D
ND
Mishizen
A
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D016895:Culture Media, Serum-Free; D018491:Dopamine Agonists / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology*
D000975:Antioxidants; D016895:Culture Media, Serum-Free; D018491:Dopamine Agonists; D018377:Neurotransmitter Agents; D011189:Potassium Chloride