| 作成者 |
|
|
|
|
|
|
|
|
|
|
|
|
|
| 本文言語 |
|
| 出版者 |
|
| 発行日 |
|
| 収録物名 |
|
| 巻 |
|
| 開始ページ |
|
| 終了ページ |
|
| 出版タイプ |
|
| アクセス権 |
|
| 関連DOI |
|
|
|
| 概要 |
In mammals, including humans, MTH1 with 8-oxo-dGTPase and OGG1 with 8-oxoguanine DNA glycosylase minimize 8-oxoguanine accumulation in genomic DNA. We investigated age-related alterations in behavior,... 8-oxoguanine levels, and neurogenesis in the brains of Mth1/Ogg1-double knockout (TO-DKO), Ogg1-knockout, and human MTH1-transgenic (hMTH1-Tg) mice. Spontaneous locomotor activity was significantly decreased in wild-type mice with age, and females consistently exhibited higher locomotor activity than males. This decrease was significantly suppressed in female but not male TO-DKO mice and markedly enhanced in female hMTH1-Tg mice. Long-term memory retrieval was impaired in middle-aged female TO-DKO mice. 8-Oxoguanine accumulation significantly increased in nuclear DNA, particularly in the dentate gyrus (DG), subventricular zone (SVZ) and major island of Calleja (ICjM) in middle-aged female TO-DKO mice. In middle-aged female TO-DKO mice, neurogenesis was severely impaired in SVZ and DG, accompanied by ICjM and DG atrophy. Conversely, expression of hMTH1 efficiently suppressed 8-oxoguanine accumulation in both SVZ and DG with hypertrophy of ICjM. These findings indicate that newborn neurons from SVZ maintain ICjM in the adult brain, and increased accumulation of 8-oxoguanine in nuclear DNA of neural progenitors in females is caused by 8-oxo-dGTP incorporation during proliferation, causing depletion of neural progenitors, altered behavior, and cognitive function changes with age.続きを見る
|
Mendeley出力
PRONEU1613_manuscript_accepted