Stimulation of adult hippocampal neurogenesis by physical exercise and enriched environment is disturbed in a CADASIL mouse model

被引：16

作者：

Klein, C. ^{[1
]}

Schreyer, S. ^{[1
]}

Kohrs, F. E. ^{[1
]}

Elhamoury, P. ^{[1
]}

Pfeffer, A. ^{[1
]}

Munder, T. ^{[1
]}

Steiner, B. ^{[1
]}

机构：

[1] Charite, Dept Neurol, Berlin, Germany

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

AUTOSOMAL-DOMINANT ARTERIOPATHY; WHITE-MATTER PATHOLOGY; SUBCORTICAL INFARCTS; CELL-PROLIFERATION; WATER MAZE; NOTCH3; NEURONS; PERFORMANCE; IMPAIRMENT; EXPRESSION;

D O I：

10.1038/srep45372

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In the course of CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a dysregulated adult hippocampal neurogenesis has been suggested as a potential mechanism for early cognitive decline. Previous work has shown that mice overexpressing wild type Notch3 and mice overexpressing Notch3 with a CADASIL mutation display impaired cell proliferation and survival of newly born hippocampal neurons prior to vascular abnormalities. Here, we aimed to elucidate how the long-term survival of these newly generated neurons is regulated by Notch3. Knowing that adult neurogenesis can be robustly stimulated by physical exercise and environmental enrichment, we also investigated the influence of such stimuli as potential therapeutic instruments for a dysregulated hippocampal neurogenesis in the CADASIL mouse model. Therefore, young-adult female mice were housed in standard (STD), environmentally enriched (ENR) or running wheel cages (RUN) for either 28 days or 6 months. Mice overexpressing mutated Notch3 and developing CADASIL (TgN3(R169C)), and mice overexpressing wild type Notch3 (TgN3(WT)) were used. We found that neurogenic stimulation by RUN and ENR is apparently impaired in both transgenic lines. The finding suggests that a disturbed neurogenic process due to Notch3-dependent micromilieu changes might be one vascular-independent mechanism contributing to cognitive decline observed in CADASIL.

引用

页数：10

共 38 条

[1] Notch1 Is Required for Maintenance of the Reservoir of Adult Hippocampal Stem Cells [J].