# AGING, CALCIUM, AND BRAIN MEMBRANE CHOLESTEROL DOMAINS

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 1993 · $177,268

## Abstract

The overall goals of this grant application are to study potential
mechanisms associated with regulation of neuronal transbilayer and lateral
cholesterol domains and how cholesterol domains interact with calcium
homeostasis in neuronal membranes of different age groups of mice. We have
recently shown in synaptic plasma membranes (SPM) of young C57BL mice,
that the two membrane leaflets are asymmetric in their fluidity and
cholesterol distribution. Membrane cholesterol was also found to be
located in exchangeable and non-exchangeable pools and membrane
cholesterol domains could be altered by hydrolysis of sphingomyelin that
also altered intracellular calcium. Preliminary data from out laboratory
showed that the asymmetry of fluidity between the two SPM leaflets
observed in 6 month old animals was significantly reduced in SPM of 28
month old animals and that the exofacial leaflet was more affected as
compared to the cytofacial leaflet. Previous studies on membrane lipid
structure in different age groups of animals have examined changes in the
average fluidity of the membrane lipid structure, whereas other studies
have not observed age differences. We propose that increasing age is
associated with marked changes in membrane lipid structure but that such
changes are occurring in specific lipid domains and changes in lipid
domains contribute to modification of calcium homeostasis that has been
previously shown to differ with increasing age. The proposed experiments
will focus on SPM and synaptosomes of 4, 16, and 28 month old C57BL/NNia
mice. The specific aims of this application are to: 1) determine
transbilayer distribution of cholesterol in the SPM exofacial and
cytofacial leaflets; 2) examine cholesterol lateral domains in SPM; 3)
phospholipid distribution in SPM exofacial and cytofacial leaflets; 4)
involvement of sphingomyelin in regulation of cholesterol domains; 5)
brain sterol carrier proteins and regulation of cholesterol domains; and
6) cholesterol domains and presynaptic calcium. It is our working
hypothesis that aging impairs the capacity of the membrane to regulate
cholesterol domains and such changes in cholesterol domains modify
neuronal calcium.

## Key facts

- **NIH application ID:** 3123046
- **Project number:** 1R01AG011056-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **SAM.gov UEI:** KABJZBBJ4B54
- **Principal Investigator:** WELLINGTON GIBSON WOOD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $177,268
- **Award type:** 1
- **Project period:** 1993-09-30 → 1997-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123046

## Citation

> US National Institutes of Health, RePORTER application 3123046, AGING, CALCIUM, AND BRAIN MEMBRANE CHOLESTEROL DOMAINS (1R01AG011056-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123046. Licensed CC0.

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