| Item type |
学位論文 / Thesis or Dissertation(1) |
| 公開日 |
2010-02-22 |
| タイトル |
|
|
タイトル |
Respective roles of isoforms of glutamic acid decarboxylase in GABA synthesis and neuronal function |
| タイトル |
|
|
タイトル |
Respective roles of isoforms of glutamic acid decarboxylase in GABA synthesis and neuronal function |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_46ec |
|
資源タイプ |
thesis |
| 著者名 |
季, 鳳雲
|
| フリガナ |
キ, ホウウン
|
| 著者 |
JI, Feng Yun
|
| 学位授与機関 |
|
|
|
学位授与機関名 |
総合研究大学院大学 |
| 学位名 |
|
|
学位名 |
博士（学術） |
| 学位記番号 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
総研大甲第416号 |
| 研究科 |
|
|
値 |
生命科学研究科 |
| 専攻 |
|
|
値 |
20 生理科学専攻 |
| 学位授与年月日 |
|
|
学位授与年月日 |
1999-03-24 |
| 学位授与年度 |
|
|
値 |
1998 |
| 要旨 |
|
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内容記述タイプ |
Other |
|
内容記述 |
γ -Aminobutyric acid (GABA) is a principal inhibitory neurotransmitter in the mammalian central nervous system. GABA is almost exclusively synthesized through α-decarboxylation of L-glutamic acid by GAD, which is expressed in GABAergic neurons. Mammalian GAD has two isoforms, GAD65 and GAD67, which are named after their molecular masses of 65 and 67 kDa, and encoded by two independent genes respectively. Several different properties of these isoforms have been demonstrated but their distinct roles in GABA synthesis have not been clarified. <br /> To disclose different functions of GAD65 and GAD67, GABA contents and GAD expressions together with histology and animal behavior were analyzed in mice carrying null mutations for either GAD65 or GAD67 and the both. GAD65 mutant mice were studied over 4 months after birth. The tissues were subjected to organotypic culture from GAD67-deficient mice which did not survive after birth. <br /> GABA contents were significantly increased after 2 months of wild type mice in the amygdala, cerebral cortex, and hypothalamus. On the other hand, GABA contents were unchanged over 4 months in GAD65-deficient mice. GAD65-deficient mice also showed several behavioral abnormalities, i. e, increase in sensitivity to convulsants, anxiety, and freezing to fear and decrease in intermale aggression. <br /> GABA contents of hippocampus and cerebellum in GAD67 null mutant mice were less than 5% of those in the wild-type mice on the first day after birth. After 14 days in culture, GAD65 protein and GABA contents were markedly increased in GAD67 null mutant hippocampus and cerebellum. The proteins of GAD65 and GAD67 and GABA contents were extensively increased during the culture in GAD67+/+ and GAD67+/- mice. The observation that expressions of GAD65 was not different between the genotypes indicates that upregulation of the GAD65 expresson did not occur in the absence of GAD67. Histological studies showed that GABA-containing fiber networks well developed during culture. <br /> In order to study GAD-independent GABA synthesis and neuronal development in extreme GABA deficiency, mice lacking both isoforms of GAD were generated. GABA was almost undetectable in GAD65/GAD67-deficient mice but these mice did not show any discernible disorders of histogenesis. <br /> These results indicate that the two isoforms of GAD have distinct roles in GABA synthesis: GABA is mainly generated by GAD67 during prenatal development. While GAD65 is not required in the young mice, it is crucial for the adult. Although trophic functions of GABA have been suggested, our results indicate that deficits in GABA have no influence on neurogenesis in GAD mutant mice. |
| 所蔵 |
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|
値 |
有 |
| フォーマット |
|
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内容記述タイプ |
Other |
|
内容記述 |
application/pdf |
要旨・審査要旨 / Abstract, Screening Result (231.0 kB)
