Aldhshan, M. S., Mizuno, T. M. 2022. Effect of environmental enrichment on aggression and the expression of brain-derived neurotrophic factor transcript variants in group-housed male mice. Behavioural Brain Research 433, 113986.

Social and environmental factors influence behavior via modulation of brain physiological functions. Environmental enrichment (EE) is an animal housing technique that provides complex sensory, motor, and social stimulation, leading to modifications in the innate aggressiveness in group-housed laboratory mice. Brain-derived neurotrophic factor (BDNF) is encoded by multiple splice variants and plays a critical role in controlling aggressive behavior in a transcript variant-specific manner. BDNF mediates the beneficial effects of EE on a variety of pathophysiological conditions. These findings led to the hypothesis that EE reduces aggressive behavior by altering the expression of Bdnf mRNA in a transcript variant-specific manner. To test this hypothesis, 3–4-week-old male C57BL/6 mice were randomly group-housed (5 mice per cage) under standard or EE conditions for 6–8 weeks. Aggressive behavior was monitored and levels of Bdnf mRNA variants in aggression-related brain regions were measured. Mice housed in EE cages displayed a significantly lower frequency of aggressive interactions compared to control mice. EE increased levels of Bdnf mRNA variant I (Bdnf I) in the amygdala while it reduced levels of Bdnf I in the hypothalamus, hippocampus, prefrontal cortex, parietal cortex, and brainstem. Meanwhile, EE did not significantly alter levels of Bdnf mRNA variants IIc, IV, and VI in all brain regions examined. These findings support the hypothesis that EE diminishes inter-male aggression by altering Bdnf mRNA expression in a transcript variant-specific and brain region-specific manner. Specifically, brain region-specific alterations in Bdnf I expression may partly mediate EE-induced suppression of inter-male aggression.