本日はRei Nagata (国際基督教大学4年生)が以下の論文を紹介しました。当研究室に所属して初めてのジャーナルクラブ担当でした。
Cell Rep. 2018 Feb 20;22(8):1974-1981. doi: 10.1016/j.celrep.2018.02.001.
Tet2 Rescues Age-Related Regenerative Decline and Enhances Cognitive Function in the Adult Mouse Brain.
Gontier G1, Iyer M1, Shea JM1, Bieri G1, Wheatley EG2, Ramalho-Santos M3, Villeda SA4.
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Abstract
Restoring adult stem cell function provides an exciting approach for rejuvenating the aging brain. However, molecular mechanisms mediating neurogenic rejuvenation remain elusive. Here we report that the enzyme ten eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes the production of 5-hydroxymethylcytosine (5hmC), rescues age-related decline in adult neurogenesis and enhances cognition in mice. We detected a decrease in Tet2 expression and 5hmC levels in the aged hippocampus associated with adult neurogenesis. Mimicking an aged condition in young adults by abrogating Tet2 expression within the hippocampal neurogenic niche, or adult neural stem cells, decreased neurogenesis and impaired learning and memory. In a heterochronic parabiosis rejuvenation model, hippocampal Tet2 expression was restored. Overexpressing Tet2 in the hippocampal neurogenic niche of mature adults increased 5hmC associated with neurogenic processes, offset the precipitous age-related decline in neurogenesis, and enhanced learning and memory. Our data identify Tet2 as a key molecular mediator of neurogenic rejuvenation.
Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
KEYWORDS:
Tet2; adult neurogenesis; aging; cognition; hippocampus; hydroxymethylation; rejuvenationPMID: 29466726 PMCID: PMC5870899 DOI: 10.1016/j.celrep.2018.02.001
