Investigation of transcriptomic changes (RNA-seq) in the RVM in the context of social stress

• Grant number: 25/11424-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2025
• End date: July 31, 2029
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marco Oreste Finocchio Pagliusi Junior
• Grantee: Geovana Agostinho de Amorim
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 22/06332-4 - Rostral ventromedial medulla: what is its role in behavioral changes induced by social stress?, AP.GR

Abstract

Major depressive disorder (MDD) affects a significant portion of the global population and is primarily diagnosed based on criteria established by the Diagnostic and Statistical Manual of Mental Disorders (DSM). Although chronic pain is not listed among the symptoms of depression in the DSM, epidemiological studies have indicated a strong association between depressive disorders and chronic pain. The social defeat stress model is currently used to induce depression-like behaviors and persistent hyperalgesia in mice. In this model, mice are exposed for 10 consecutive days to an aggressive conspecific from a physically stronger strain, undergoing brief periods of physical aggression followed by longer periods of visual and olfactory contact. Notably, chronic pain induced by this model resembles human fibromyalgia, a condition characterized by widespread chronic pain and closely linked to depression.The experience of pain, in all its complexity, involves the perception of various factors integrated by the central nervous system (CNS), especially the cerebral cortex. This integrative process is highly dynamic and is constantly adjusted to daily demands. Pain begins with the activation of peripheral nociceptors, which send ascending neural signals to higher levels of the CNS through specific neural pathways. These ascending pathways are modulated by a series of supraspinal descending pathways, which act as endogenous systems for either pain inhibition or facilitation.A key brain structure involved in descending pain modulation is the rostral ventromedial medulla (RVM). The RVM plays a central role in both the facilitatory and inhibitory control of pain, receiving projections from several brain regions such as the periaqueductal gray (PAG), nucleus accumbens, and anterior cingulate cortex. Unsurprisingly, these same neural structures are also implicated in depressive behavior. Previous data have demonstrated the involvement of the RVM in pain induced by social stress and, interestingly, in depression-like behaviors resulting from social stress. These findings have raised new questions and inspired the development of the present project. Therefore, the aim of this proposal is to investigate transcriptomic alterations in the RVM and its projections in the context of social stress. (AU)