PhD Scientific Days 2024

Poster Session D - Neurosciences 1.

Genomic insights into the effects of social isolation on the medial prefrontal cortex in male rats

Text of the abstract

According to the theory of homeostatic regulation of social behaviors, short social deprivation increases social interactions. However, the neural mechanisms of this regulation remain unknown. The medial prefrontal cortex (mPFC) plays a pivotal role in the regulation of social behavior in vertebrates. Consequently, we postulated that it may also play a role in social homeostasis. To investigate this, we assessed the impact of social isolation on gene expression in the mPFC using RNA sequencing method (RNA-seq) in male rats housed in pairs or solitarily for 10 days. To characterize the behavioral effects of social isolation, the social, anxiety- and depression-like behaviors of the animals were measured using three-chamber, elevated plus maze and forced swim tests, respectively. The isolated animals exhibited reduced sociability and social novelty preference, but increased social interaction and heightened locomotion. There was no change in their aggression, anxiety, or depression-like activity. Transcriptomics analysis revealed differential expression of 46 genes between the groups, some with known or predicted social functions. Based on the KEGG pathway analysis, differentially expressed genes play a key role in neuroactive ligand-receptor interaction, particularly the dopaminergic and peptidergic systems and addiction. Subsequent validation confirmed the decreased level of three altered genes: Regulator of G Protein Signalling 9 (Rgs9), Serotonin Receptor 2c (Htr2c), and Prodynorphin (Pdyn), which are involved in dopaminergic, serotonergic, and peptidergic function, respectively. Antagonizing Htr2c confirmed its role in social novelty discrimination. The findings imply that 10 days of social isolation can significantly affect gene expression affecting monoaminergic and peptidergic systems of the mPFC, which furthers our understanding of the effects of social isolation at the molecular level.

Grant support was provided by NAP3 project of the HAS (NAP2022-I-3/2022), the NKFIH OTKA K134221, OTKA K146077, TKP2021-EGA/TKP2021- NVA/TKP2021-NKTA, EFOP-3.6.3-VEKOP-16-2017-00009 and TKP2021-EGA-25 grants. New National Excellence Program and Doctoral Student Scholarship Program of the Co-operative Doctoral Program of NKFIH, and the Gedeon Richter Plc. Centenary Foundation.