Telencephalon-specific Alkbh1 conditional knockout mice display hippocampal atrophy and impaired learning.

Autor: Kawarada L; Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan.; Department of Biological Sciences, School of Science, The University of Tokyo, Japan., Fukaya M; Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Japan., Saito R; Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan., Kassai H; Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan., Sakagami H; Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Japan., Aiba A; Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan.; Department of Biological Sciences, School of Science, The University of Tokyo, Japan.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2021 Jun; Vol. 595 (12), pp. 1671-1680. Date of Electronic Publication: 2021 May 19.
DOI: 10.1002/1873-3468.14098
Abstrakt: AlkB homolog 1 (ALKBH1) is responsible for the biogenesis of 5-formylcytidine (f 5 C) on mitochondrial tRNA Met and essential for mitochondrial protein synthesis. The brain, especially the hippocampus, is highly susceptible to mitochondrial dysfunction; hence, the maintenance of mitochondrial activity is strongly required to prevent disorders associated with hippocampal malfunction. To study the role of ALKBH1 in the hippocampus, we generated dorsal telencephalon-specific Alkbh1 conditional knockout (cKO) mice in inbred C57BL/6 background. These mice showed reduced activity of the respiratory chain complex, hippocampal atrophy, and CA1 pyramidal neuron abnormalities. Furthermore, performances in the fear-conditioning and Morris water maze tests in cKO mice indicated that the hippocampal abnormalities led to impaired hippocampus-dependent learning. These findings indicate critical roles of ALKBH1 in the hippocampus.
(© 2021 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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