# AQP4 isoforms and brain edema

> **NIH NIH R21** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $471,749

## Abstract

Gap junctions and Aquaporin4 (AQP4) water channels form a water distribution network that is crucial for brain
water homeostasis and for generation of water movements hypothesized to drive the glymphatic circulation.
Despite their importance, fundamental issues remain to be resolved regarding the nature of the channels
formed by AQP4 and its newly discovered isoforms and the interdependence of gap junction and AQP4
distribution in astrocytes. We here propose to determine function and structure of novel AQP4 isoforms and
interactions with gap junction plaques using transfected cells and transgenic mouse models that were newly
generated by the MPIs. One particular focus will be on the AQP4 isoforms that aggregate into Orthologal
Arrays of Particles (OAPs) in astrocyte endfeet and are believed to provide most water flux. Because AQP4
channels and gap junctions are primarily in the endfeet of astrocytes, they provide control of brain water
homeostasis. We will test the hypothesis that changes in AQP4 OAPs correlate with changes in gap junction
plaque structure/distribution and that the permeability of blood-brain-barrier (BBB) is modified by this interplay
between the astrocyte AQP4 isoforms and gap junction plaques. We expect that these straightforward
studies using methods routine in our laboratories on new mouse models will provide key fundamental
information on the organization of AQP4 isoforms in astrocyte endfeet relative to gap junction plaques and on
the functions of AQP4 isoforms and gap junctions in BBB regulation. This proposal represents a collaboration
between groups of investigators who have published several studies together and is expected to provide the
foundation for future studies aimed to understand the cellular mechanisms involved in the redistribution of
water, ions and solutes mediated by the combined action of AQP4 and gap junctions.
.

## Key facts

- **NIH application ID:** 9984034
- **Project number:** 1R21NS116892-01
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Antonio Frigeri
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $471,749
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984034

## Citation

> US National Institutes of Health, RePORTER application 9984034, AQP4 isoforms and brain edema (1R21NS116892-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9984034. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*