Shaw · Physiology & behavior 2024 · controlled laboratory animal experiment · n=32 mice (15 males, 17 females)

Chronic corticosterone administration alters synaptic mitochondrial function within the hippocampus of C57Bl/6NTac mice.

Level 5 - mechanism / opinion, no new human data

Animal research

PubMed 39209050 · doi:10.1016/j.physbeh.2024.114681 · record verified 2026-08-26

What was done

Adult male (n = 15) and female (n = 17) C57Bl/6NTac mice received vehicle or corticosterone (CORT; 35 µg/mL) in drinking water for 21 consecutive days. Researchers assessed fluid intake, piloerection, plasma and fecal corticosterone concentrations, and behavior (including Y-maze navigation and anxiety-like behavior). Synaptosomes were isolated from the hippocampus to measure mitochondrial respiration parameters (basal respiration, maximal respiration, proton leak, and ATP production) using an Agilent Cell Mito Stress test.

What was found

CORT-containing water consumption was similar between sexes, but elevated circulating plasma and fecal corticosterone levels and increased piloerection occurred only in males. In both sexes, CORT decreased direct revisits in the Y-maze, without producing anxiety-like behavior. In hippocampal synaptosomes, chronic CORT caused a decrease in basal respiration, maximal respiration, proton leak, and ATP production in both male and female mice. Specific numerical values and statistical test statistics were not reported in the abstract.

Why it matters

These findings indicate that chronic stress hormone exposure can disrupt hippocampal synaptic bioenergetics across sexes, demonstrating that neural metabolic changes can occur even when peripheral corticosterone elevations are undetectable in females.

Limits

The study was conducted in a small rodent cohort (n = 32) and lacks human clinical validation. The abstract reports directional findings without exact numerical values, effect sizes, or confidence intervals. Mechanisms explaining why neural deficits occurred in females without measurable peripheral corticosterone increases remain unaddressed.

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