# MICROGLIAL BIOLOGY--AGE-RELATED RESPONSE TO LESIONS

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 1993 · $157,779

## Abstract

The current proposal focuses on functional changes in immune/neural system
interactions that impact on post-injury cellular plasticity.  The short-
term goal of these studies is to chronicle the basic mechanisms underlying
age-related microglial changes in the normal degenerative/regenerative
process over the life-span in a rodent model. The integration of these
findings with studies of Alzheimer's disease currently underway could
determine if microglia and their secretory products, along with beta-
amyloid protein precursor (beta-APP) and its breakdown products, may work
synergistically in a neurodegenerative cascade.

The hypothesis underlying this proposal is that microglia mediate the
degenerative/regenerative processes that follow deafferentation and
axotomy, and that this is altered in the aged animal. Three Specific Aims
have been devised to test this hypothesis. Specific Aim 1 involves a
series of descriptive studies designed to fully characterize microglial
anatomy, expression of markers reflective of activation, and production of
secretory products in young, middle-aged and old mice. Specific Aim 2 will
examine microglial responses to two different types of lesions
(deafferentation and axotomy) with increasing age. Anatomical changes
reflective of cellular plasticity, expression of microglial triggers and
markers reflective of microglial activation, production of microglial
secretory products, and the production and fate of beta-APP will be
analyzed. Finally, Specific Aim 3 will manipulate elements of these
responses in isolated microglial primary cell cultures derived from the
various age and lesion experimental groups. The expression of markers
reflective of microglial activation, production of microglial secretory
products, and microglial proliferation and phagocytosis will be examined.
These Specific Aims will be investigated using quantitative light and
electron microscopy, polymerase chain reaction-based analyses, in situ
hybridization, lesioning, primary cell culture, and combinations of these
techniques. The proposed studies should provide insights into the types of
changes that may underlie age-related, abnormal brain function.

## Key facts

- **NIH application ID:** 3123111
- **Project number:** 1R01AG011126-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **SAM.gov UEI:** G88KLJR3KYT5
- **Principal Investigator:** CHRIS ZAROW
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $157,779
- **Award type:** 1
- **Project period:** 1993-08-05 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123111

## Citation

> US National Institutes of Health, RePORTER application 3123111, MICROGLIAL BIOLOGY--AGE-RELATED RESPONSE TO LESIONS (1R01AG011126-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123111. Licensed CC0.

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