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Immunity & Ageing

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Open Access 01-12-2022 | Cytokines | Research

Sex differences in inflammation in the hippocampus and amygdala across the lifespan in rats: associations with cognitive bias

Authors: Travis E. Hodges, Stephanie E. Lieblich, Rebecca K. Rechlin, Liisa A. M. Galea

Published in: Immunity & Ageing | Issue 1/2022

Abstract

Background

Cognitive symptoms of major depressive disorder, such as negative cognitive bias, are more prevalent in women than in men. Cognitive bias involves pattern separation which requires hippocampal neurogenesis and is modulated by inflammation in the brain. Previously, we found sex differences in the activation of the amygdala and the hippocampus in response to negative cognitive bias in rats that varied with age. Given the association of cognitive bias to neurogenesis and inflammation, we examined associations between cognitive bias, neurogenesis in the hippocampus, and cytokine and chemokine levels in the ventral hippocampus (HPC) and basolateral amygdala (BLA) of male and female rats across the lifespan.

Results

After cognitive bias testing, males had more IFN-γ, IL-1β, IL-4, IL-5, and IL-10 in the ventral HPC than females in adolescence. In young adulthood, females had more IFN-γ, IL-1β, IL-6, and IL-10 in the BLA than males. Middle-aged rats had more IL-13, TNF-α, and CXCL1 in both regions than younger groups. Adolescent male rats had higher hippocampal neurogenesis than adolescent females after cognitive bias testing and young rats that underwent cognitive bias testing had higher levels of hippocampal neurogenesis than controls. Neurogenesis in the dorsal hippocampus was negatively associated with negative cognitive bias in young adult males.

Conclusions

Overall, the association between negative cognitive bias, hippocampal neurogenesis, and inflammation in the brain differs by age and sex. Hippocampal neurogenesis and inflammation may play greater role in the cognitive bias of young males compared to a greater role of BLA inflammation in adult females. These findings lay the groundwork for the discovery of sex-specific novel therapeutics that target region-specific inflammation in the brain and hippocampal neurogenesis.

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Title: Sex differences in inflammation in the hippocampus and amygdala across the lifespan in rats: associations with cognitive bias
Authors: Travis E. Hodges
Stephanie E. Lieblich
Rebecca K. Rechlin
Liisa A. M. Galea
Publication date: 01-12-2022
Publisher: BioMed Central
Keyword: Cytokines
Published in: Immunity & Ageing / Issue 1/2022
Electronic ISSN: 1742-4933
DOI: https://doi.org/10.1186/s12979-022-00299-4

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