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題名 Enhanced GDNF mRNA expression upon (-)-deprenyl and melatonin treatment.
作者 趙知章
YP, Tang;YL, Ma;CC, Chao;EHY, Lee
貢獻者 神科所
關鍵詞 glial cell line-derived neurotrophic factor;1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine;(−)-deprenyl; GM1 ganglioside;melatonin; gene expression;striatum
日期 1998
上傳時間 13-Jul-2016 14:30:49 (UTC+8)
摘要 Glial cell line-derived neurotrophic factor (GDNF) has been shown to be a preferentially selective neurotrophic factor for dopamine (DA) neurons. In the present study, we have examined the distribution of GDNF mRNA expression in several major DA-containing cell body and terminal areas and the regulation of GDNF mRNA expression upon various pharmacological treatments. Results indicated that there is a relatively higher GDNF mRNA level in neurons of the nigrostriatal and mesolimbic dopaminergic pathways. Upon chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment (30 mg/kg, i.p., for 7 days), DA level was decreased, whereas GDNF mRNA expression was increased in the striatum, suggesting that more GDNF is synthesized and expressed to cope with the neurotoxin insult. Furthermore, among several DA neuron protective and/or therapeutic agents examined, both intrastriatal injections of (−)-deprenyl (1.25 μg and 2.5 μg) and melatonin (30 μg, 60 μg, and 120 μg) significantly enhanced GDNF mRNA expression in the striatum, whereas the same concentrations of (−)-deprenyl did not affect monoamine oxidase B (MAOB) activity, although it increased glutathione peroxidase (GPx) and/or superoxide dismutase (SOD) activities. Similarly, the same concentrations of melatonin did not alter SOD or GPx activities, except that the highest dose of melatonin (120 μg) increased lipid peroxidation in the striatum. Conversely, GM1 ganglioside injection (45 μg) lacked of an effect on GDNF mRNA expression. Together, these results suggest that both (−)-deprenyl and melatonin up-regulate GDNF gene expression at threshold doses lower than that needed for altering MAOB activity and/or the antioxidant enzyme systems, respectively. These results provide new information on the neuroprotective and therapeutic mechanisms of (−)-deprenyl and melatonin on DA neurons. J. Neurosci. Res. 53:593–604, 1998. © 1998 Wiley-Liss, Inc.
關聯 J. Neurosci. Res., 53(5), 593-604
資料類型 article
DOI http://dx.doi.org/10.1002/(SICI)1097-4547(19980901)53:5<593::AID-JNR9>3.0.CO;2-4
dc.contributor 神科所
dc.creator (作者) 趙知章zh_TW
dc.creator (作者) YP, Tang;YL, Ma;CC, Chao;EHY, Lee
dc.date (日期) 1998
dc.date.accessioned 13-Jul-2016 14:30:49 (UTC+8)-
dc.date.available 13-Jul-2016 14:30:49 (UTC+8)-
dc.date.issued (上傳時間) 13-Jul-2016 14:30:49 (UTC+8)-
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/99015-
dc.description.abstract (摘要) Glial cell line-derived neurotrophic factor (GDNF) has been shown to be a preferentially selective neurotrophic factor for dopamine (DA) neurons. In the present study, we have examined the distribution of GDNF mRNA expression in several major DA-containing cell body and terminal areas and the regulation of GDNF mRNA expression upon various pharmacological treatments. Results indicated that there is a relatively higher GDNF mRNA level in neurons of the nigrostriatal and mesolimbic dopaminergic pathways. Upon chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment (30 mg/kg, i.p., for 7 days), DA level was decreased, whereas GDNF mRNA expression was increased in the striatum, suggesting that more GDNF is synthesized and expressed to cope with the neurotoxin insult. Furthermore, among several DA neuron protective and/or therapeutic agents examined, both intrastriatal injections of (−)-deprenyl (1.25 μg and 2.5 μg) and melatonin (30 μg, 60 μg, and 120 μg) significantly enhanced GDNF mRNA expression in the striatum, whereas the same concentrations of (−)-deprenyl did not affect monoamine oxidase B (MAOB) activity, although it increased glutathione peroxidase (GPx) and/or superoxide dismutase (SOD) activities. Similarly, the same concentrations of melatonin did not alter SOD or GPx activities, except that the highest dose of melatonin (120 μg) increased lipid peroxidation in the striatum. Conversely, GM1 ganglioside injection (45 μg) lacked of an effect on GDNF mRNA expression. Together, these results suggest that both (−)-deprenyl and melatonin up-regulate GDNF gene expression at threshold doses lower than that needed for altering MAOB activity and/or the antioxidant enzyme systems, respectively. These results provide new information on the neuroprotective and therapeutic mechanisms of (−)-deprenyl and melatonin on DA neurons. J. Neurosci. Res. 53:593–604, 1998. © 1998 Wiley-Liss, Inc.
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dc.relation (關聯) J. Neurosci. Res., 53(5), 593-604
dc.subject (關鍵詞) glial cell line-derived neurotrophic factor;1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine;(−)-deprenyl; GM1 ganglioside;melatonin; gene expression;striatum
dc.title (題名) Enhanced GDNF mRNA expression upon (-)-deprenyl and melatonin treatment.
dc.type (資料類型) article
dc.identifier.doi (DOI) 10.1002/(SICI)1097-4547(19980901)53:5<593::AID-JNR9>3.0.CO;2-4
dc.doi.uri (DOI) http://dx.doi.org/10.1002/(SICI)1097-4547(19980901)53:5<593::AID-JNR9>3.0.CO;2-4