Rats Selected for Different Nervous Excitability: Long-Term Emotional-Painful Stress Affects the Dynamics of DNA Damage in Cells of Several Brain Areas.

The maintenance of genome stability is critical for health, but during individual ontogenesis, different stressors affect DNA integrity, which can lead to functional and/or structural changes in the cells of target organs. In the nervous system, cell genome destabilization is associated with different neurological and psychiatric diseases, but experiments in vivo, where a link between stress and DNA instability has been demonstrated, are relatively rare. Here, we use rat strains selected for the contrast excitability of the tibialis nerve (n. tibialis) and nonselected Wistar rats to investigate the reasons for individual differences in developing post-stress pathologies. Previous research on the behavioral response of these strains to prolonged emotional-painful stress (PEPS) allows us to consider one strain as a model of post-traumatic stress disorder (PTSD) and another strain as a model of compulsive disorder (CD). We study DNA damage in the cells of the prefrontal cortex (PFC), hippocampus, and amygdala, regions involved in stress responses and the formation of post-stress dysfunctions. The evaluation of cell genome integrity via the comet assay shows different responses to PEPS in each brain area analyzed and for all strains used. This could help us to understand the reasons for individual differences in the consequences of stress and the pathophysiology of post-stress disease formation.

Pheromone of grouped female mice impairs genome stability in male mice through stress-mediated pathways.

Population density is known to affect the health and survival of many species, and is especially important for social animals. In mice, living in crowded conditions results in the disruption of social interactions, chronic stress, and immune and reproductive suppression; however, the underlying mechanisms remain unclear. Here, we investigated the role of chemosignals in the regulation of mouse physiology and behavior in response to social crowding. The pheromone 2,5-dimethylpyrazine (2,5-DMP), which is released by female mice in crowded conditions, induced aversion, glucocorticoid elevation and, when chronic, resulted in reproductive and immune suppression. 2,5-DMP olfaction induced genome destabilization in bone marrow cells in a stress-dependent manner, providing a plausible mechanism for crowding-induced immune dysfunction. Interestingly, the genome-destabilizing effect of 2,5-DMP was comparable to a potent mouse stressor (immobilization), and both stressors led to correlated expression changes in genes regulating cellular stress response. Thus, our findings demonstrate that, in mice, the health effects of crowding may be explained at least in part by chemosignals and also propose a significant role of stress and genome destabilization in the emergence of crowding effects.