Alcohol's effects on the mouse brain are modulated by age and sex

Abstract

Binge alcohol consumption is common among adolescents and may impair normal brain development. Emerging, longitudinal studies in adolescents suggest that the effects of binge alcohol exposure on brain structure differ between sexes. To test the hypothesis that the effects of binge alcohol exposure on developmental brain growth trajectories are influenced by age of exposure and sex, adolescent and adult, male and female C57Bl/6 mice (n = 32), were exposed to a binge-like ethanol (EtOH) exposure paradigm (i.e., 5 cycles of 2 on/2 off days of 5 g/kg EtOH intraperitoneal) or served as saline controls. Longitudinal structural magnetic resonance imaging was acquired at baseline, following binge EtOH exposure, and after 2 weeks of recovery. Alcohol treatment showed interactions with age and sex in altering whole brain volume: adolescents of both sexes demonstrated inhibited whole brain growth relative to their control counterparts, although significance was only attained in female mice which showed a larger magnitude response to EtOH compared to male mice. In region of interest analyses, the somatosensory cortex and cerebellum showed inhibited growth in male and female adolescent mice exposed to EtOH, but the difference relative to controls did not reach multiple comparison-corrected statistical significance. These data suggest that in mice exposed to binge EtOH treatment, adolescent age of exposure and female sex may confer a higher risk to the detrimental effects of EtOH on brain structure and reinforce the need for direct testing of both sexes.

Keywords: adolescent; alcohol; binge drinking; brain volume; sex.

FIGURE 1

Mean ± S.E.M. body weight in adolescents and adults (columns), males and females (rows), in EtOH‐treated (line) and control (dash) mice

FIGURE 2

(left) Mean ± S.E.M. whole brain volume in adolescents and adults (columns), males and females (rows), in EtOH‐treated (line) and control (dash) mice. (right) Grand averages of axial MR images of four animals in each group (i.e., adolescent female and male mice; adult female and male mice) at baseline and after treatment with ethanol. Visual inspection indicates that male are larger than female, and adult are larger than the adolescent brains

FIGURE 3

Mean ± S.E.M. cerebellar cortex (left) and somatosensory cortex (right) volumes in adolescents and adults (columns), males and females (rows), in EtOH‐treated (line) and control (dash) mice. (bottom) Sample axial slices from the Allen Mouse Brain Atlas indicating the two regions exhibiting volume growth delay in adolescent female mice following ethanol exposure