Hippocampal neurogenesis in the adult brain is thought to play a role in learning, memory and cognition. Decline in cognitive performance during aging is attributed, in part, to reduced neurogenesis. Further, neurogenesis is impaired in aging-linked cognitive disorders. However, the mechanisms compromising neurogenesis in aging are not fully elucidated. Caveolin-1 (Cav-1) is the principal component of caveolae. Cav- 1 is known to play a major role in the function of endothelial cells. Here we show that Cav-1 is expressed in hippocampal neural progenitor cells. Deletion of Cav-1 leads to reduced number of neural stem cells in the hippocampus of Cav-1 knockout mice. Neurospheres derived from the hippocampus of Cav-1 KO are significantly smaller, compared to Cav-1 wild type. The expression of the neurogenic receptors epidermal growth factor, fibroblast growth factor, bone morphogenetic protein 1 a receptor, and insulin growth factor 1 receptor, is altered in Cav-1 KO neurospheres, and may underlie proliferation impairments. This study will test the hypothesis that depletion of Caveolin-1 in neural stem and progenitor cells downregulates proliferation by compromising the metabolism of neurogenic signaling receptors. Using NestinCreERT2;Cav- 1loxlox mice, Aim 1 will determine the effect of Cav-1 depletion on hippocampal neurogenesis.
Aim 2 will determine the effect of Cav-1 depletion on the metabolism of neurogenic receptors. This study will establish the role of Cav-1 as a critical regulator of adult hippocampal neurogenesis.

Public Health Relevance

The mechanisms underlying decline in neurogenesis during aging are not fully elucidated. This project describes caveolin-1 as a novel regulator of hippocampal neurogenesis. Depletion of caveolin-1 may compromise neurogenesis during brain aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AG061628-02
Application #
9876965
Study Section
Neurogenesis and Cell Fate Study Section (NCF)
Program Officer
Dibattista, Amanda
Project Start
2019-03-01
Project End
2021-02-28
Budget Start
2020-05-15
Budget End
2021-02-28
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612