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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

Sexually divergent induction of microglial-associated neuroinflammation with hippocampal aging

Authors: Colleen A. Mangold, Benjamin Wronowski, Mei Du, Dustin R. Masser, Niran Hadad, Georgina V. Bixler, Robert M. Brucklacher, Matthew M. Ford, William E. Sonntag, Willard M. Freeman

Published in: Journal of Neuroinflammation | Issue 1/2017

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Abstract

Background

The necessity of including both males and females in molecular neuroscience research is now well understood. However, there is relatively limited basic biological data on brain sex differences across the lifespan despite the differences in age-related neurological dysfunction and disease between males and females.

Methods

Whole genome gene expression of young (3 months), adult (12 months), and old (24 months) male and female C57BL6 mice hippocampus was analyzed. Subsequent bioinformatic analyses and confirmations of age-related changes and sex differences in hippocampal gene and protein expression were performed.

Results

Males and females demonstrate both common expression changes with aging and marked sex differences in the nature and magnitude of the aging responses. Age-related hippocampal induction of neuroinflammatory gene expression was sexually divergent and enriched for microglia-specific genes such as complement pathway components. Sexually divergent C1q protein expression was confirmed by immunoblotting and immunohistochemistry. Similar patterns of cortical sexually divergent gene expression were also evident. Additionally, inter-animal gene expression variability increased with aging in males, but not females.

Conclusions

These findings demonstrate sexually divergent neuroinflammation with aging that may contribute to sex differences in age-related neurological diseases such as stroke and Alzheimer’s, specifically in the complement system. The increased expression variability in males suggests a loss of fidelity in gene expression regulation with aging. These findings reveal a central role of sex in the transcriptomic response of the hippocampus to aging that warrants further, in depth, investigations.
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Metadata
Title
Sexually divergent induction of microglial-associated neuroinflammation with hippocampal aging
Authors
Colleen A. Mangold
Benjamin Wronowski
Mei Du
Dustin R. Masser
Niran Hadad
Georgina V. Bixler
Robert M. Brucklacher
Matthew M. Ford
William E. Sonntag
Willard M. Freeman
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-0920-8

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