PPARγ activation in N2A cells and neurodegenerative disease

• Main Authors: Chen-Fong Huang, 黃承鋒
• Other Authors: Kun-Ruey Shieh
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/76431545622471797122

碩士 === 慈濟大學 === 生理暨解剖醫學碩士班 === 99 === It has been demonstrated that PPARγ agonists reduce neuronal cell loss in in vitro models of neurotoxicity and in in vivo models of Alzheimer's Disease, Parkinson’s disease and amyotrophic lateral sclerosis. In this study, we treat rosiglitazone three days in the first and then we treat rosiglitazone fifty-six days to investigate the neuron cells’ morphology and whether it has neuroprotective effects. At last, we investigate what PPARγ plays the neuroprotective role in neurodegenerative disease. In this study, we also use Huntington's disease's (HD) transgenic mice model. HD is an autosomal dominant hereditary neurodegenerative disease caused by a CAG trinucleotide repeats exceptional expansion of exon 1 of the Huntingtin (Htt) gene. HD is due to brain neurons continued to degenerate, resulting in nervous system signaling some areas serious dysfunction. HD will attack the brain neurons, also particularly the cerebellum and hippocampus specific. In the brain of the HD mice, the baseline levels of PPARγ and mitochondrial genes (PGC-1α, NRF-1, NRF-2 and Tfam) mRNA were reduced and then we use TZD treatment, PPARγ and mitochondrial genes (PGC-1α, NRF-1, NRF-2 and Tfam) mRNA were recoverd. The baseline levels of Bcl-2, HSP-60, HSP-70 proteins were also reduced in HD mice. We use TZD treatment also recoverd in HD mice. Therefore, this study investigate the activation of PPARγ in HD mice brain of mitochondrial function, which may be an important therapeutic approach to improve brain damage in HD symptoms.