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Effect of the peroxisome proliferator-activated receptor beta activator GW0742 in rat cultured cerebellar granule neurons.
- Source :
-
Journal of neuroscience research [J Neurosci Res] 2004 Jul 15; Vol. 77 (2), pp. 240-9. - Publication Year :
- 2004
-
Abstract
- The ligand-activated transcription factor peroxisome proliferator-activated receptor beta (PPARbeta) is present in the brain and is implicated in the regulation of genes with potential roles in neurotoxicity. We sought to examine the role of PPARbeta in neuronal cell death by using the PPARbeta ligand GW0742. Primary cultures of rat cerebellar granule neurons were prepared from 7-day-old pups. Reverse transcriptase-polymerase chain reaction and in situ hybridization were used to verify that PPARbeta mRNA was present in neurons. After 10-12 days in culture, the neuronal cells were incubated in the presence of GW0742, and cell death was measured with a lactate dehydrogenase release (LDH) assay. After 24 hr of exposure, PPARbeta activation by GW0742 was not inherently toxic to cerebellar granule neurons. However, toxicity was observed after 48 hr, with cell death mediated via an apoptotic mechanism. In an effect opposite to that observed with PPARalpha-activating ligands, PPARbeta activation exhibited neuroprotective properties. Treatment with GW0742 significantly reduced cell death during a 12-hr exposure to low-KCl media. These results clearly reinforce very specific roles for the PPAR isoforms in neurons and suggest that PPARbeta is worthy of further investigation regarding its potential role as a therapeutic target in neurodegenerative states.<br /> (Copyright 2004 Wiley-Liss, Inc.)
- Subjects :
- Animals
Animals, Newborn
Cell Death drug effects
Cells, Cultured
Cerebellum cytology
Cerebellum drug effects
Cerebellum metabolism
L-Lactate Dehydrogenase drug effects
L-Lactate Dehydrogenase metabolism
Nerve Degeneration chemically induced
Neurons drug effects
Neurotoxins antagonists & inhibitors
Neurotoxins metabolism
Potassium Deficiency metabolism
Proto-Oncogene Proteins c-jun drug effects
Proto-Oncogene Proteins c-jun metabolism
Pyrimidines pharmacology
RNA, Messenger drug effects
RNA, Messenger metabolism
Rats
Rats, Sprague-Dawley
Receptors, Cytoplasmic and Nuclear agonists
Receptors, Cytoplasmic and Nuclear genetics
Transcription Factors agonists
Transcription Factors genetics
Cell Death physiology
Nerve Degeneration metabolism
Neurons metabolism
Receptors, Cytoplasmic and Nuclear metabolism
Thiazoles pharmacology
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0360-4012
- Volume :
- 77
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of neuroscience research
- Publication Type :
- Academic Journal
- Accession number :
- 15211590
- Full Text :
- https://doi.org/10.1002/jnr.20153