Gene expression profiles underlying aggressive behavior in the prefrontal cortex of cattle

Abstract

Aggressive behavior is an ancient and conserved trait considered habitual and essential for most animals in order to eat, protect themselves from predators and also to compete for mating and defend their territories. Genetic factors have shown to play an important role in the development of aggression both in animals and humans, displaying moderate to high heritability estimates. However, although such types of conducts have been studied in different animal models, the molecular architecture of aggressiveness remains poorly understood. This study compared gene expression profiles of 16 prefrontal cortex (PFC) samples from aggressive and non-aggressive cattle breeds: Lidia, selected for agonistic responses, and Wagyu, specialized on meat production and selected for tameness. RNA sequencing was used to identify 918 up and 278 down-regulated differentiated expressed genes (DEG). The functional interpretation of the up-regulated genes in the aggressive cohort revealed enrichment of pathways such as the Alzheimer disease-presenilin, integrins or the ERK/MAPK signaling cascade, all implicated in the development of abnormal aggressive behaviors and neurophysiological disorders. Moreover, gonadotropins, leading to testosterone release, are also up-regulated as natural mechanisms enhancing aggression. Concomitantly, heterotrimeric G-protein pathways, associated with low reactivity mental states, and the GAD2 gene, a repressor of agonistic reactions at PFC, are down-regulated, guaranteeing the development of the adequate responses required by the aggressive Lidia cattle. We also identified six upstream regulators, whose functional activity fits with the etiology of abnormal behavioral responses associated with aggression. These results provide valuable insights into the complex architecture that underlie naturally developed agonistic behaviors.