# Role of ependyma in forebrain homeostasis

> **NIH NIH R01** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2020 · $324,661

## Abstract

Project Description
The high probability of breakdown in the functioning of the central nervous system (CNS) during late stages of
aging, as in Alzheimer’s disease and various dementias is a major concern for the elderly. Triggers that initiate
age-associated diseases and neurological conditions are for the most part unknown. A key to these
associations could be the population of ependymal cells in the brain. Ependymal cells form a monolayer that
functions as a barrier between the cerebrospinal fluid (CSF) and the overlying cellular compartments of the
brain. As such, they regulate CSF production, circulation, and filtering, and thus ependymal cells are a key
component of the newly described ‘glymphtic-lymphatic’ system. This system is purported to control CSF-
vascular interactions in the brain parenchyma and thus contribute to the overall clearance of the brain of
toxicants and metabolic byproducts and allow entry of immune cells into the brain. The ependymal layer
appears damaged in the aged brain, yet whether the damage is caused by malfunctioning signals in the
overlying CNS tissue, or if ependymal damage causes defects in neurons and glia in the CNS remain
unknown. We have developed several genetic mouse models which suggest the ependymal layer may be the
root of many problems in the brain interstitium related to various neurodegenerative diseases and during
normal aging in the CNS. We will use these models to study this novel concept. Studies in our mouse models
have revealed a previously unknown expression and clearance of mucins by ependymal cells in the CNS.
Since mucins function to protect against inflammation and infectious diseases in other tissues, our results have
led to the central hypothesis that mucin secretion by ependymal cells is required for maintenance and
functional integrity of homeostasis in the forebrain during aging, and that disruption of mucin secretion can lead
to aberrant function and disease in the CNS. Our project uses a variety of genetic mice, together with cellular,
molecular, and biochemical approaches to test our hypothesis.
Potential for Broader Impact: Our approaches to understand how aging affects the brain through its
monolayer of ependymal cells have wide implications. Disruption of filtration and protective functions of
ependymal cells may be the root of a range of pathological conditions that emerge during late stages of aging.
Therefore, undertaking the basic cellular mechanisms that control aging of the brain is critical to understanding
not only how healthy aging may be controlled by ependymal cells, but also how abnormalities in ependymal
aging may lead to devastating diseases such as Alzheimer’s. Moreover, the mechanisms we study can be
harnessed to develop novel aging therapeutics by targeting ependymal functions selectively.

## Key facts

- **NIH application ID:** 9899335
- **Project number:** 5R01NS098370-05
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Hooman Troy Ghashghaei
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $324,661
- **Award type:** 5
- **Project period:** 2016-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899335

## Citation

> US National Institutes of Health, RePORTER application 9899335, Role of ependyma in forebrain homeostasis (5R01NS098370-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9899335. Licensed CC0.

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