Social isolation, but not partner separation, lowers hippocampal synaptosome mitochondrial respiration in female California mice (Peromyscus californicus)

Social isolation, loneliness, and loss profoundly impact health and quality of life, but the complex nature of these constructs can prohibit mechanistic examination in rodent models. Assessment of the peripheral and neural effects of environment manipulations in a social rodent species, such as California mice (Peromyscus californicus), can facilitate inquiry into the biological repercussions of experiencing different types of loss. Stressors can compromise neural function in the hippocampus and a portion of this effect is due to deficits in mitochondrial function at the synapse. Mitochondria at the synapse are essential to facilitate neural transmission and compromise can impair neurotransmission and thereby behavior. In the current study, we used genetically monogamous male and female California mice to evaluate synaptic mitochondrial respiration following removal of a same-sex cage mate for 10- or 30-days (i.e., social isolation; Experiment 1) OR a 10-day separation from an opposite-sex partner following 10-days of cohabitation (i.e., partner separation; Experiment 2). In the social isolation cohort, males, but not females, exhibited physical changes consistent with a prolonged stress response, including reduction in body mass and hypertrophy of the adrenal glands following isolation. In contrast, isolated female mice demonstrated a reduction in hippocampal synaptic mitochondrial respiration at both 10- and 30-days following social isolation, compared to females that remained pair-housed. No effects were observed in males. Social isolation did not alter open field outcomes for either sex. We then investigated the impact of separation from an opposite sex partner on the same metrics. Separation from an opposite sex partner was qualitatively less impactful, such that there were no statistically significant changes observed in body mass, adrenal weight, open field behavior, or mitochondrial respiration following separation from an opposite sex mate. Collectively, these data suggest that males and females differentially manifest the impact of social stress on synaptic mitochondria respiration.