Age influences aggressive behaviour: an RNA-seq analysis in bovines

Aggressiveness is one of our most basic behaviors, characterized by targeted intentional actions oriented to cause harm or damage. The reactive type of aggression is regulated mainly in the brain prefrontal cortex; however, the molecular changes underlying aggressiveness in adults have not been fully characterized. Here we used a RNA-seq approach to investigate differential gene expression in the prefrontal cortex of bovines from the aggressive Lidia breed at different age stages: young three-year old and adult four-year-old bulls. The number of up and down-regulated genes in the adult group were 50 and 193, respectively. These genes were associated with diverse functions, including neural plasticity and behavior. A cross-species comparative analysis retrieved 29 genes in common with previous studies on aggressive behaviors. Particularly, we detected changes in the regulation of networks such as the synaptogenesis, involved in the synapses maintenance and refinement, and the glutamate receptor pathway, which acts as excitatory driver in aggression responses. Furthermore, the Wnt//β-catenin signaling pathway was present in both up and down-regulated genes in the adult group, and has been implicated in adult altered behaviors and cognitive disorders. At the regulatory level, we identified four upstream regulators, all involved in behavioral processes and neuropsychiatric disorders including aggressive demonstrations. Our results on an animal model in which the aging process enhance the intensity of aggressive responses provide, for the first time, insights into candidate genes and networks involved in the molecular mechanisms leading to the maturation of the brain, with a focus on cattle agonistic components.