# The role of autophagy in the neurovascular unit for the physiological response to stress.

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $437,812

## Abstract

PROJECT SUMMARY
Macroautophagy (MA) is a cellular response to stress whose dysfunction is implicated in several
neurodegenerative diseases. Our limited understanding about how MA is used by distinct CNS cell types has
hindered our ability to fully understand the implications of its dysfunction for CNS diseases. A fundamental and
well-defined physiologic stress linked to MA is acute nutrient starvation. In vertebrates, starvation-induced
activation of MA in peripheral organs such as liver, heart and muscle is essential for maintaining amino acid
and glucose blood levels. However, prolonged MA results in loss of organ mass, ultimately leading to
breakdown and irreparable damage of these vital organs. It has long been appreciated that under conditions of
prolonged starvation, peripheral organs are sacrificed to maintain brain function; however, the mechanisms
remain poorly understood. In contrast to most cells in the body, neurons receive nutrients indirectly from the
blood through a tightly coordinated signalling with endothelial cells (ECs), pericytes and astrocytes that
collective form the neurovascular unit (NVU). Given the critical role that these cells play in forming the blood-
brain barrier (BBB), that tightly regulates the influx of nutrients into the brain, they are likely to be highly
sensitive to the nutrient status of the periphery, and play a key role in prioritizing the brain during starvation. In
this proposal, we will test the hypothesis that MA is upregulated in astrocytes upon starvation and plays a
central role in triggering an essential, positive-feedback loop with brain ECs to maintain neuronal function
during physiologic starvation. In Aim 1, we will characterize the metabolic function of mice lacking MA in discrete CNS
cell types. In Aim 2 we will establish the autophagic response to starvation in astrocytes and how this influences
ECs. Upon successful completion of the proposed studies, we will gain new understanding into the molecular
and cell-specific response of MA in NVU cells of the CNS before and during starvation, and how they
coordinate their efforts to ensure that neuronal function is maintained. In addition to gaining insight into this
important and critical physiologic response, these studies will provide conceptual and methodological
advances regarding how discrete cell types of the CNS use MA during conditions of stress and disease.

## Key facts

- **NIH application ID:** 10072565
- **Project number:** 1R21NS118891-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Dritan Agalliu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $437,812
- **Award type:** 1
- **Project period:** 2020-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072565

## Citation

> US National Institutes of Health, RePORTER application 10072565, The role of autophagy in the neurovascular unit for the physiological response to stress. (1R21NS118891-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10072565. Licensed CC0.

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