※ をクリックすると外部の論文のサイトが開きます。
論文
- タイトル
- タイトル（英）
- Minocycline prevents early age-related cognitive decline in a mouse model of intellectual disability caused by ZBTB18/RP58 haploinsufficiency.
- 参照URL
- https://researchmap.jp/tomoko-t/published_papers/48251874
- 著者
- 著者（英）
- Tomoko Tanaka,Shinobu Hirai,Hiroyuki Manabe,Kentaro Endo,Hiroko Shimbo,Yasumasa Nishito,Junjiro Horiuchi,Hikari Yoshitane,Haruo Okado
- 担当区分
- 筆頭著者, 責任著者
- 概要
- 概要（英）
- Haploinsufficiency of the transcriptional repressor ZBTB18/RP58 is associated with intellectual disability. However, the mechanisms causing this disability are unknown, and preventative measures and treatments are not available. Here, we assessed multiple behaviors in Zbtb18/Rp58 heterozygous-knockout mice, and examined local field potentials, DNA fragmentation, mitochondrial morphology, and performed histochemical and transcriptome analyses in the hippocampus to evaluate chronic inflammation. In wild-type mice, object location memory was present at a similar level at 2 and 4-5 months of age, and became impaired at 12-18 months. In contrast, Zbtb18/Rp58 heterozygous-knockout mice displayed early onset impairments in object location memory by 4-5 months of age. These mice also exhibited earlier accumulation of DNA and mitochondrial damage, and activated microglia in the dentate gyrus, which are associated with defective DNA repair. Notably, chronic minocycline therapy, which has neuroprotective and anti-inflammatory effects, attenuated age-related phenotypes, including accumulation of DNA damage, increased microglial activation, and impairment of object location memory. Our results suggest that Zbtb18/Rp58 activity is required for DNA repair and its reduction results in DNA and mitochondrial damage, increased activation of microglia, and inflammation, leading to accelerated declines in cognitive functions. Minocycline has potential as a therapeutic agent for the treatment of ZBTB18/RP58 haploinsufficiency-associated cognitive dysfunction.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Journal of neuroinflammation
- 巻
- 21
- 号
- 1
- 開始ページ
- 260
- 終了ページ
- 260
- 出版年月
- 2024年10月12日
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1186/s12974-024-03217-1
- 共同研究・競争的資金等の研究課題