The role of different Homer1 isoforms in acute and chronic social stress

Homer proteins are scaffolds that interact with metabotrobic glutamate receptors and bind to Ca²⁺ signaling proteins at synapses. Homer1, a subtype of the Homer protein family, has been implicated in the processing of novel experiences and memory formation in animal studies, whereas clinical studies suggest an association of SNPs in the Homer1 gene with major depression. Our study aims to unravel the role of two major Homer1 isoforms, Homer1a and Homer1b/c, in the mediation of responses to chronic and acute social stress. We therefore investigated the regulation of Homer1 on both mRNA and protein level and its interaction with stress-associated behavioral phenotypes. Our results show that chronic social defeat stress has a pronounced impact on both the animals' neuroendocrine profile and their behavior. Accompanying these findings, Homer1b/c mRNA levels are increased following chronic social defeat stress, while Homer1a gene expression did not change. On the other hand, Homer1a transcription was induced 1 hour after a single defeat and was followed by a decline in Homer1b/c mRNA expression 4 hours after the stressor. These findings suggest an important role of Homer1 modulating the effects of social stress. Future investigations will be directed towards the manipulation of the glutamate system in conjunction with social stress to further elucidate the role of Homer1 in the stress response.