Shh from mossy cells contributes to preventing NSC pool depletion after seizure-induced neurogenesis and in aging

Author:

Noguchi Hirofumi1ORCID,Arela Jessica Chelsea1,Ngo Thomas1,Cocas Laura12,Pleasure Samuel13ORCID

Affiliation:

1. Department of Neurology, University of California, San Francisco

2. Santa Clara University, Biology Department, Neuroscience Program

3. Programs in Neuroscience and Developmental & Stem Cell Biology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco

Abstract

Epileptic seizures induce aberrant neurogenesis from resident neural stem cells (NSCs) in the dentate gyrus of the adult mouse hippocampus, which has been implicated in depletion of the NSC pool and impairment of hippocampal function. However, the mechanisms regulating neurogenesis after seizures remain unknown. Here, we demonstrate that Sonic hedgehog (Shh) from mossy cells is a major source of Shh signaling activity after seizures, by which mossy cells contribute to seizure-induced neurogenesis and maintenance of the NSC pool. Deletion of Shh from mossy cells attenuates seizure-induced neurogenesis. Moreover, in the absence of Shh from mossy cells, NSCs pool are prematurely depleted after seizure-induced proliferation, and NSCs have impaired self-renewal. Likewise, lack of Shh from mossy cells accelerates age-related decline of the NSC pool with accompanying reduction of self-renewal of NSCs outside the context of pathology such as seizures. Together, our findings indicate that Shh from mossy cells is critical to maintain NSCs and to prevent exhaustion from excessive consumption in aging and after seizures.

Funder

National Institutes of Health

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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