Age-Dependent Remarkable Regenerative Potential of the Dentate Gyrus Provided by Intrinsic Stem Cells

Show full item record



Permalink

http://hdl.handle.net/10138/327411

Citation

Licht , T , Kreisel , T , Biala , Y , Mohan , S , Yaari , Y , Anisimov , A , Alitalo , K & Keshet , E 2020 , ' Age-Dependent Remarkable Regenerative Potential of the Dentate Gyrus Provided by Intrinsic Stem Cells ' , Journal of Neuroscience , vol. 40 , no. 5 , pp. 974-995 . https://doi.org/10.1523/JNEUROSCI.1010-19.2019

Title: Age-Dependent Remarkable Regenerative Potential of the Dentate Gyrus Provided by Intrinsic Stem Cells
Author: Licht, Tamar; Kreisel, Tirzah; Biala, Yoav; Mohan, Sandesh; Yaari, Yoel; Anisimov, Andrey; Alitalo, Kari; Keshet, Eli
Contributor: University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, HUSLAB
Date: 2020-01-29
Language: eng
Number of pages: 22
Belongs to series: Journal of Neuroscience
ISSN: 0270-6474
URI: http://hdl.handle.net/10138/327411
Abstract: Multiple insults to the brain lead to neuronal cell death, thus raising the question to what extent can lost neurons be replenished by adult neurogenesis. Here we focused on the hippocampus and especially the dentate gyrus (DG), a vulnerable brain region and one of the two sites where adult neuronal stem cells (NSCs) reside. While adult hippocampal neurogenesis was extensively studied with regard to its contribution to cognitive enhancement, we focused on their underestimated capability to repair a massively injured, nonfunctional DG. To address this issue, we inflicted substantial DG-specific damage in mice of either sex either by diphtheria toxin-based ablation of >50% of mature DG granule cells (GCs) or by prolonged brain-specific VEGF overexpression culminating in extensive, highly selective loss of DG GCs (thereby also reinforcing the notion of selective DG vulnerability). The neurogenic system promoted effective regeneration by increasing NSCs proliferation/survival rates, restoring a nearly original DG mass, promoting proper rewiring of regenerated neurons to their afferent and efferent partners, and regaining of lost spatial memory. Notably, concomitantly with the natural age-related decline in the levels of neurogenesis, the regenerative capacity of the hippocampus also subsided with age. The study thus revealed an unappreciated regenerative potential of the young DG and suggests hippocampal NSCs as a critical reservoir enabling recovery from catastrophic DG damage.
Subject: adult neurogenesis
dentate gyrus
hippocampal plasticity
neural stem cells
regeneration
VEGF
ENDOTHELIAL GROWTH-FACTOR
NEURAL STEM
HIPPOCAMPAL NEUROGENESIS
MEMORY DEFICITS
GRANULE CELLS
DEGENERATION
DYSFUNCTION
DEPLETION
INJURY
MICE
3112 Neurosciences
3124 Neurology and psychiatry
3111 Biomedicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
974.full.pdf 16.08Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record