# Signaling pathways regulating hippocampal neurogenesis in the adult mouse

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $199,875

## Abstract

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.

## Key facts

- **NIH application ID:** 9876965
- **Project number:** 5R21AG061628-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Orly Lazarov
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $199,875
- **Award type:** 5
- **Project period:** 2019-03-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876965

## Citation

> US National Institutes of Health, RePORTER application 9876965, Signaling pathways regulating hippocampal neurogenesis in the adult mouse (5R21AG061628-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9876965. Licensed CC0.

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