2022年4月
Deficiency of MTH1 and/or OGG1 increases the accumulation of 8-oxoguanine in the brain of the AppNL-G-F/NL-G-F knock-in mouse model of Alzheimer’s disease, accompanied by accelerated microgliosis and reduced anxiety-like behavior
Neuroscience Research
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- 巻
- 177
- 号
- 開始ページ
- 118
- 終了ページ
- 134
- 記述言語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.neures.2021.11.009
- 出版者・発行元
- Elsevier {BV}
Oxidative stress is a major risk factor for Alzheimer's disease (AD). Among various oxidized molecules, the marked accumulation of an oxidized form of guanine, 8-oxo-7,8-dihydroguanine (8-oxoG), is observed in the AD brain. 8-oxo-2′-deoxyguanosine triphosphatase (MTH1) and 8-oxoG DNA glycosylase (OGG1) minimize the 8-oxoG accumulation in DNA, and their expression is decreased in the AD brain. MTH1 and/or OGG1 may suppress the pathogenesis of AD; however, their exact roles remain unclear. We evaluated the roles of MTH1 and OGG1 during the pathogenesis of AD using AppNL-G-F/NL-G-F knock-in mice (a preclinical AD model). Six-month-old female AppNL-G-F/NL-G-F mice with MTH1 and/or OGG1 deficiency exhibited reduced anxiety-related behavior, but their cognitive and locomotive functions were unchanged; the alteration was less evident in 12-month-old mice. MTH1 and/or OGG1 deficiency accelerated the 8-oxoG accumulation and microgliosis in the amygdala and cortex of six-month-old mice; the alteration was less evident in 12-month-old mice. Astrocytes and neurons were not influenced. We showed that MTH1 and OGG1 are essential for minimizing oxidative DNA damage in the AppNL-G-F/NL-G-F brain, and the effects are age-dependent. MTH1 and/or OGG1 deficiency reduced anxiety-related behavior in AppNL-G-F/NL-G-F mice with a significant acceleration of the 8-oxoG burden and microgliosis, especially in the cortex and amygdala.
- リンク情報
-
- DOI
- https://doi.org/10.1016/j.neures.2021.11.009 本文へのリンクあり
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/34838904
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85120420645&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85120420645&origin=inward
- ID情報
-
- DOI : 10.1016/j.neures.2021.11.009
- ISSN : 0168-0102
- eISSN : 1872-8111
- ORCIDのPut Code : 103777092
- PubMed ID : 34838904
- SCOPUS ID : 85120420645