# GLIAL-NEURONAL INTERACTIONS IN NEURODENGENERATION

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 1991 · $164,831

## Abstract

Progressive neuronal degeneration underlies the cognitive dysfunction of
Alzheimer's disease (AD).  The neuritic plaque, consisting of deposits of
Beta-amyloid (BetaA4) protein surrounded by reactive glia and degenerating
neurons, is a hallmark of AD.  Given the role of astrocytes (glial cells)
in regulating the development and viability of neurons, the goal of this
project is to test the hypothesis that abnormal glial-neuronal interactions
influence neurodegeneration by altering neuronal Ca2+ homeostasis.  One
series of experiments will utilize the trisomy 16 (Ts16) mouse which
contains an extra copy of chromosome 16, on which is located the gene
coding for Beta-amyloid precursor protein (BetaAPP) and the mouse homolog
of the putative familial AD locus.  In order to test whether increased
expression of one or more chromosome 16 genes affects neuronal properties,
the effects of astrocytes and astrocyte-derived substances on the viability
and structure of hippocampal neurons will be studied in vitro by co-
culturing various combinations of Ts16 and euploid neurons and astrocytes,
by examining effects of Ts16 and euploid astrocyte-conditioned medium on
neuronal properties, and by adding various putative glial-derived growth
factors and their neutralizing antibodies to the neuronal cultures.  The
role of intracellular Ca2+ in the premature death of Ts16 neurons in
culture will be examined by computer-assisted imaging of ionized internal
Ca2+ levels in Ts16 and euploid neurons using the fluorescent Ca2+
indicator, fura-2.  A second series of experiments will study S100Beta, a
Ca2+-binding protein widely distributed in brain in man, that is elevated
in AD.  S100Beta has been reported to have both neurotrophic and glial
mitogenic activity.  In order to test the hypothesis that excessive levels
of S100Beta may overstimulate neuronal process formation, making the neuron
more vulnerable to a loss of intracellular Ca2+ regulation, cultured
hippocampal neurons from normal mice will be studied in the presence of
S100Beta or anti-S100Beta antibodies.  Neuronal viability and neurite
configuration will be evaluated.  The effects of S100Beta overexpression on
astrocyte structure, function, and development will be investigated in
cultured hippocampal astrocytes from transgenic S100Beta mice and in
sections of transgenic S100Beta mouse brain.  In addition, regulation of
neuronal and astrocyte intracellular CA2+ in the presence of S100Beta will
be studied by imaging of fura-2 fluorescence.

## Key facts

- **NIH application ID:** 3122642
- **Project number:** 1R01AG010686-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **SAM.gov UEI:** Z9CRZKD42ZT1
- **Principal Investigator:** BRUCE KARL KRUEGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $164,831
- **Award type:** 1
- **Project period:** 1991-09-29 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122642

## Citation

> US National Institutes of Health, RePORTER application 3122642, GLIAL-NEURONAL INTERACTIONS IN NEURODENGENERATION (1R01AG010686-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122642. Licensed CC0.

---

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