MPTP로 유도된 파킨슨병 동물 모델에서 에틸 피루브산의 도파민성 신경세포사멸 억제 효과에 대한 연구

Alternative Title
Suehee Huh
Author(s)
Suehee Huh
Alternative Author(s)
Suehee Huh
Advisor
진병관, 백은주
Department
일반대학원 의학과
Publisher
The Graduate School, Ajou University
Publication Year
2012-02
Language
eng
Keyword
Parkinson`s diseaseMPTPEthyl pyruvategliaROSNeurotrophic factors
Alternative Abstract
The present study examined whether ethyl pyruvate (EP) promotes the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. MPTP induced degeneration of nigrostriatal DA neurons and glial activation as visualized by tyrosine hydroxylase, macrophage antigen complex-1, and/or glial fibrillary acidic protein immunoreactivity. Western blotting and immunohistochemistry showed activation of microglial NADPH oxidase and astroglial myeloperoxidase (MPO), and subsequent reactive oxygen species (ROS)/reactive nitrogen species (RNS) production and oxidative DNA damage in the MPTP-treated substantia nigra. Additional immunohistochemical staining also showed that MPTP induced glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) in the substantia nigra (SN). Interestingly, treatment with EP prevented degeneration of nigrostriatal DA neurons, increased striatal dopamine levels, and improved motor function. This neuroprotection afforded by EP was associated with the suppression of astroglial MPO expression, NADPH oxidase- and/or inducible nitric oxide synthase-derived ROS/RNS production by activated microglia. In parallel, treatment of EP significantly increased GDNF and CNTF in the MPTP-treated SN. Also, EP was found to protect DA neurons from 1-methyl-4-phenyl-pyridinium (MPP+) neurotoxicity in co-cultures of mesencephalic neurons and glia, but not in neuron-enriched mesencephalic cultures devoid of glia. The present findings show that EP may inhibit oxidative stress and increase levels of neurotrophic factors in glia, suggesting that EP may have therapeutic value in the treatment of aspects of Parkinson’s disease related to glia activation.
URI
https://dspace.ajou.ac.kr/handle/2018.oak/17867
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Graduate School of Ajou University > Department of Medicine > 3. Theses(Master)
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