Research Paper|Volume 7, Issue 6|pp 435—449

Premature aging of the hippocampal neurogenic niche in adult Bmal1‐ deficient mice

Amira A. H. Ali¹, Beryl Schwarz‐Herzke¹, Anna Stahr¹, Timour Prozorovski², Orhan Aktas², Charlotte von Gall¹

¹Institute for Anatomy II, Medical Faculty, Heinrich Heine University, D‐40225, Düsseldorf, Germany
²Department of Neurology, Medical Faculty, Heinrich Heine University, D‐40225 Düsseldorf, Germany

Received: March 12, 2015Accepted: June 20, 2015Published: June 27, 2015

Copyright: © 2015 Ali et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Hippocampal neurogenesis undergoes dramatic age‐related changes. Mice with targeted deletion of the clock gene Bmal1 (Bmal1^‐/‐) show disrupted regulation of reactive oxygen species homeostasis, accelerated aging, neurodegeneration and cognitive deficits. As proliferation of neuronal progenitor/precursor cells (NPCs) is enhanced in young Bmal1^‐/‐ mice, we tested the hypothesis that this results in premature aging of hippocampal neurogenic niche in adult Bmal1^‐/‐ mice as compared to wildtype littermates. We found significantly reduced pool of hippocampal NPCs, scattered distribution, enhanced survival of NPCs and an increased differentiation of NPCs into the astroglial lineage at the expense of the neuronal lineage. Immunoreaction of the redox sensitive histone deacetylase Sirtuine 1, peroxisomal membrane protein at 70kDa and expression of the cell cycle inhibitor p21 Waf1/CIP1 were increased in adult Bmal1^‐/‐ mice. In conclusion, genetic disruption of the molecular clockwork leads to accelerated age‐dependent decline in adult neurogenesis presumably as a consequence of oxidative stress.