期刊
EMBO JOURNAL
卷 39, 期 21, 页码 -出版社
WILEY
DOI: 10.15252/embj.2020104472
关键词
adult neurogenesis; aging; dendrite; hippocampus; Wnt signaling
资金
- German Research Foundation [LI 858/6-3, LI 858/9-1, INST 410/45-1 FUGG]
- Bavarian Research Network ForIPS
- Bavarian Research Network ForINTER
- University Hospital Erlangen (IZKF) [E12, E16, E21]
- Deutsche Forschungsgemeinschaft [270949263/DFG GRK2162/1]
- Projekt DEAL
In adult hippocampal neurogenesis, stem/progenitor cells generate dentate granule neurons that contribute to hippocampal plasticity. The establishment of a morphologically defined dendritic arbor is central to the functional integration of adult-born neurons. We investigated the role of canonical Wnt/beta-catenin signaling in dendritogenesis of adult-born neurons. We show that canonical Wnt signaling follows a biphasic pattern, with high activity in stem/progenitor cells, attenuation in immature neurons, and reactivation during maturation, and demonstrate that this activity pattern is required for proper dendrite development. Increasing beta-catenin signaling in maturing neurons of young adult mice transiently accelerated dendritic growth, but eventually produced dendritic defects and excessive spine numbers. In middle-aged mice, in which protracted dendrite and spine development were paralleled by lower canonical Wnt signaling activity, enhancement of beta-catenin signaling restored dendritic growth and spine formation to levels observed in young adult animals. Our data indicate that precise timing and strength of beta-catenin signaling are essential for the correct functional integration of adult-born neurons and suggest Wnt/beta-catenin signaling as a pathway to ameliorate deficits in adult neurogenesis during aging.
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