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Activation of the peroxisome proliferator‐activated receptor‐α enhances cell death in cultured cerebellar granule cells
Author(s) -
Smith Steven A.,
May Fiona J.,
Monteith Gregory R.,
RobertsThomson Sarah J.
Publication year - 2001
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.1216
Subject(s) - cerebellum , neurotoxicity , granule cell , granule (geology) , biology , receptor , programmed cell death , microbiology and biotechnology , toxicity , endocrinology , medicine , biochemistry , central nervous system , apoptosis , dentate gyrus , paleontology
Peroxisome proliferator‐activated receptor‐α (PPARα) is a member of the steroid hormone receptor superfamily. In rodents, PPARα alters genes involved in cell cycle regulation in hepatocytes. Some of these genes are implicated in neuronal cell death. Therefore, in this study, we examined the toxicological consequence of PPARα activation in rat primary cultures of cerebellar granule neurons. Our studies demonstrated the presence of PPARα mRNA in cultures by reverse transcriptase‐polymerase chain reaction. After 10 days in vitro, cerebellar granule neuron cultures were incubated with the selective PPARα activator 4‐chloro‐6‐(2,3‐xylidino)2‐pyrimidinylthioacetic acid (Wy‐14,643). The inherent toxicity of Wy‐14,643 and the effect of PPARα activation following toxic stimuli were assessed. In these studies, neurotoxicity was induced through reduction of extracellular [KCl] from 25 mM to 5.36 mM. We observed no inherent toxicity of Wy‐14,643 (24 hr) in cultured cerebellar granule cells. However, after reduction of [KCl], cerebellar granule cell cultures incubated with Wy‐14,643 showed significantly greater toxicity than controls. These results suggest a posssible role for PPARα in augmentation of cerebellar granule neuronal death after toxic stimuli. J. Neurosci. Res. 66:236–241, 2001. © 2001 Wiley‐Liss, Inc.