Stress alters hypothalamic gene expression in adolescent male Golden hamsters

In Golden hamsters (Mesocricetus auratus), a two-week exposure to chronic social stress in adolescence causes acceleration of agonistic behavior, enhanced adult aggression, impaired waiting impulsivity, and higher food intake, body fat, and long-term increased body weight. In adult rodents, stress is accompanied by widespread alterations in gene expression in the brain. As stress is a potent modulator of both gene expression and behavior, the present research investigated possible mechanistic-related transcriptomic changes in the lateral, dorsomedial, and arcuate nucleus of the hypothalamus caused by adolescent stress using RNA Tag-sequencing, as these areas are involved in the regulation of metabolic and motivated behaviors. In each region, there were approximately 250 genes with higher expression compared to controls and 250 genes with lower expression. Many of the most significantly affected genes have been associated with metabolism and sex hormone function. For example, in the lateral hypothalamus, melanocortin 3 receptor, growth hormone releasing factor, both involved in metabolic processes, and neuropeptide VF precursor, involved in growth hormone inhibitory hormone production, were among the most increased in expression in stressed subjects. In the dorsomedial hypothalamus, neuropeptide W, involved in feeding cessation, was significantly decreased in expression in stressed animals. Across both regions, G-protein coupled receptor 50, involved in thermoregulation, sleep, and sex-related mood disorders, was significantly altered, but in opposite directions. In the arcuate nucleus, a number of blood brain barrier- and inflammation-related genes were altered as well. Furthermore, there were consistent patterns of genetic ensembles identified through gene ontology analysis and weighted gene correlation network analysis that were altered across each region. Many of these involved roles in RNA processing, DNA methylation, myelination, and synaptic organization. These findings reinforce prior behavioral, hormonal, and metabolic changes observed in this developmental model, and help guide future directions of research related to the negative consequences of early life stress.