# Synaptic mitochondrial respiration differs between the prefrontal cortex and hippocampus in female, but not male, mice: no effect of chronic stress history

## TL;DR

Chronic stress affects anxiety in both male and female mice, but only females show region-specific differences in brain mitochondrial respiration.

## Contribution

The study reveals sex-specific differences in synaptic mitochondrial respiration in the brain following chronic stress.

## Key findings

- CRPS induced anxiety-like behavior in both male and female mice.
- Females showed region-specific differences in synaptic mitochondrial respiration between the PFC and HPC.
- Females expressed higher levels of ESR2 and UCP2 in the HPC compared to males.

## Abstract

We evaluated the impact of chronic repeated predation stress (CRPS) on presentation of anxiety-like behavior and synaptic mitochondrial respiration within the prefrontal cortex (PFC) and hippocampus (HPC). Male and female C57Bl/6NTac mice were subject to CRPS for 15 days during their adolescent (PND36–50) and early adult (PND57–71) stages. All animals were assessed for anxiety-like behavior in the open-field assay in adulthood. Brains were collected (PND106–108) and immediately used to assess synaptic mitochondrial respiration with the SeahorseXFe24 instrument. CRPS induced anxiety-like behavior in both male and female mice in the open field, despite not observing stress effects on mitochondrial respiration within either sex. However, females displayed significant region-specific differences that were not reflected within the males. PFC mitochondria respiration was higher the synaptic mitochondrial respiration rates in the HPC across all mitochondrial dynamics in female, but not male, mice. To further understand regional differences in mitochondrial respiration, we analyzed expression of ESR2 and UCP2 as both are indicated in regulation of mitochondrial dynamics. In the HPC, females expressed higher levels of both genes compared to males which may contribute to regional differences in females. Further, hippocampal ESR2 expression was elevated by CRPS in both sexes, suggesting a potential mechanism by which synaptic mitochondria are protected.