Lead exposure altered stress and depression-like behavior differently in male and female mice

Different effects in male and female mice

Pregnant C57BL/6J mice received 250 parts per million lead acetate in their drinking water from gestational day 0 until their offspring reached adulthood. In the offspring, chronic lead exposure increased immobility in both the forced-swimming test and the tail-suspension test, behaviors the researchers used as measures of depression-like behavior.

Lead exposure also increased markers of oxidative stress in the prefrontal cortex and hippocampus, with differences depending on sex and brain region. After behavioral stress, males showed a delayed peak in the stress hormone corticosterone. Females showed a prolonged corticosterone response that was still elevated 24 hours later.

Why sex differences matter

The study indicates that long-term lead exposure beginning during pregnancy can affect behavior, brain redox balance—the balance between damaging and protective chemical reactions—and stress-hormone responses in mice. The sex-specific patterns suggest that biological sex is relevant when studying the effects of developmental lead exposure, although this experiment does not establish how closely the results apply to people.

Evidence and caveats

This was an experimental study in C57BL/6J mice, with lead acetate given in drinking water from pregnancy until the offspring reached adulthood. The findings come from forced-swimming and tail-suspension tests, measurements of reactive oxygen species and lipid peroxidation in two brain regions, and blood corticosterone after behavioral stress. The abstract does not report the number of mice or all sex- and region-specific results. Because the study used mice and these behavioral tests, the findings do not by themselves show that lead exposure causes depression in people or that the same hormone patterns occur in humans.