# Cell type-specific complement activation and glial reactivity in male and female mice with dietary obesity

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2023 · $394,157

## Abstract

PROJECT SUMMARY
Neuroinflammation is a shared feature of obesity and dementia, but the processes that initiate and perpetuate
glial reactivity are not well understood,. Several recent studies, including from our lab, have outlined signaling
cascades linking peripheral and central inflammation in obesity in males, but vulnerability to obesity-induced
metabolic pathology is sexually dimorphic, and susceptibility to neuroinflammation follows similar patterns. Adult
females exhibit stronger innate immunity, and evidence from clinical and experimental studies suggests that this
dimorphism involves sex differences in activation of complement. However, current understanding of tissue-
specific complement activation remains rudimentary due to the scarcity of approaches for cell type-specific
manipulation. To this end, we generated transgenic mice with inducible, cell type-specific deletion of the
endogenous complement inhibitor Crry, and will use this model to distinguish between target cells and 'bystander'
populations in the adult brain. After determining whether selective activation of complement is sufficient for
neuroinflammation, we will examine the role of sexually dimorphic complement activation as a mechanism for
differential vulnerability to synaptic and behavioral dysfunction on obesogenic diets. These themes will be
addressed using state-of-the-art methodology, including newly developed strategies for high-throughput
morphometric analysis of glial cells in cleared brains and region-specific manipulation of glial gene expression.

## Key facts

- **NIH application ID:** 10754112
- **Project number:** 1R01DK134202-01A1
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Alexis M. Stranahan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $394,157
- **Award type:** 1
- **Project period:** 2023-07-24 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10754112

## Citation

> US National Institutes of Health, RePORTER application 10754112, Cell type-specific complement activation and glial reactivity in male and female mice with dietary obesity (1R01DK134202-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10754112. Licensed CC0.

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