Redina, O. E. | Search bioRxiv

bioRxiv2024

Neurotransmitter Genes in the Nucleus Accumbens that Are Involved in the Development of Behavioral Pathology After Positive Fighting Experiences and Their Deprivation. A Conceptual Paradigm for Neurogenomic Data Analysis

It has been shown earlier that repeated positive fighting experience in daily agonistic interactions is accompanied by the development of psychosis-like behavior with signs of an addiction-like state associated with changes in the expression of genes encoding the proteins involved in the main neurotransmitter events in some brain regions of aggressive male mice. Fighting deprivation (a no-fight period of 2 weeks) causes a significant increase in their aggressiveness. This paper is aimed at studying--after a period of fighting deprivation--the involvement of genes (associated with neurotransmitter systems within the nucleus accumbens) in the above phenomena. The nucleus accumbens is known to participate in reward-related mechanisms of aggression. We found the following differentially expressed genes (DEGs), whose expression significantly differed from that in controls and/or mice with positive fighting experience in daily agonistic interactions followed by fighting deprivation: catecholaminergic genes Th, Drd1, Drd2, Adra2c, Ppp1r1b, and Maoa; serotonergic genes Maoa, Htr1a, Htr1f, and Htr3a; opioidergic genes Oprk1, Pdyn, and Penk; and glutamatergic genes Grid1, Grik4, Grik5, Grin3a, Grm2, Grm5, Grm7, and Gad1. The expression of DEGs encoding proteins of the GABAergic system in experienced aggressive male mice mostly returned to control levels after fighting deprivation except for Gabra5. In light of the conceptual paradigm for analyzing data that was chosen in our study, the aforementioned DEGs associated with the behavioral pathology can be considered responsible for consequences of aggression followed by fighting deprivation, including mechanisms of an aggression relapse.

neuroscience↗

bioRxiv2020

Reduced Expression of Slc Genes in the VTA and NAcc of Male Mice with Positive Fighting Experience

There are many psychiatric medications targeting the activity of SLC transporters. Therefore, further research is needed to elucidate the expression profiles of the Slc* genes, which may serve as markers of altered brain metabolic processes and neurotransmitter activities in psychoneurological disorders. We studied differentially expressed Slc genes using the transcriptomic profiles in the ventral tegmental area (VTA), nucleus accumbens (NAcc), and prefrontal cortex (PFC) of male mice with psychosis-like behavior induced by repeated aggression experience in daily agonistic interactions which are accompanied by wins. Most of differentially expressed Slc genes in the VTA and NAcc (12 of 17 and 25 of 26, respectively) were downregulated, which was not the case in the PFC (6 and 5, up- and down, respectively). Also, the majority of these genes were shown to have brain region-specific expression profiles. In the VTA and NAcc altered expression was observed for the genes encoding the transporters of neurotransmitters as well as inorganic and organic ions, amino acids, metals, glucose, etc. This means alteration in transport functions for many substrates, which results in complete disruption of all cellular and neurotransmitter processes. The neurotransmitter systems, especially, the dopaminergic one, in male mice with positive fighting experience in daily agonistic interactions undergo changes leading to profound genomic modifications which include downregulated expression of the majority of the Slc* genes at least in the VTA and NAcc, which is attributable to chronic stimulation of the reward systems.

neuroscience↗