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Cholinergic activation of hippocampal neural stem cells in aged dentate gyrus
Author(s) -
Itou Yoshie,
Nochi Rokuya,
Kuribayashi Hiroshi,
Saito Yu,
Hisatsune Tatsuhiro
Publication year - 2011
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20761
Subject(s) - dentate gyrus , cholinergic , hippocampal formation , neurogenesis , neuroscience , neural stem cell , hippocampus , cholinergic fibers , stimulation , cholinergic neuron , physostigmine , acetylcholine , psychology , endocrinology , biology , stem cell , microbiology and biotechnology
Adult hippocampal neurogenesis contributes to the hippocampal circuit's role in cognitive functioning. New neurons are generated from hippocampal neural stem cells (NSCs) throughout life, but their generation is substantially diminished in aged animals due to a decrease in NSC proliferation. Because acetylcholine (ACh) is an important neurotransmitter released in the hippocampus during learning and exercise that is known to decrease with aging, we investigated whether aged NSCs can respond to ACh. In this study, we found that cholinergic stimulation has a positive effect on NSC proliferation in both young adult (8–12 weeks old) and aged mice (>2 years old). In fresh hippocampal slices, we observed a rapid calcium increase in NSCs in the dentate gyrus after muscarinic cholinergic stimulation, in both age groups. Furthermore, we found that the exercise‐induced promotion of aged NSC proliferation was abrogated by the specific lesioning of the septal cholinergic system. In turn, cholinergic activation by either eserine (physostigmine) or donepezil treatment promoted the proliferation of NSCs in aged mice. These results indicate that NSCs respond to cholinergic stimulation by proliferating in aged animals. Physiological and/or pharmacological cholinergic stimulation(s) may ameliorate cognitive decline in aged animals, by supporting adult hippocampal neurogenesis. © 2010 Wiley‐Liss, Inc.