Functional lateralization of the medial prefrontal cortex in anxiety and depression in mice: molecular and psychopharmacological evaluations

• Grant number: 16/24568-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): July 01, 2017
• Effective date (End): July 31, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Ricardo Luiz Nunes de Souza
• Grantee: Nathália Santos Costa
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Stress, which can be defined as a condition that disturbs the physiological and psychological balance of an individual, is a risk factor for the development of neuropsychiatric diseases. However, not all individuals who experience a stressful event develop illnesses related to it. This is due to the existence of differences in the ability to adapt to stress, that is, the manifestation of susceptibility or resilience phenotypes.The search for an understanding of the neural systems involved in these differences has evidenced an important role of the medial prefrontal cortex (mPFC) and, more recently, its functional lateralization has gained special attention. In this sense, studies suggest that exposure to chronic stress causes damage to the left mPFC (LmPFC), decreasing its functionality and culminating in persistent maladaptive changes, being these changes modulated by the right hemisphere (RmPFC).Thus, it is possible that the inactivation of LmPFC mimics the deleterious effects of stress, increasing the individual's susceptibility. In addition, molecular alterations have also been pointed out as fundamental for the expression of resilience or susceptibility to stress, highlighting the transcription factors ”FosB and deregulation in glutamatergic neurotransmission. As humans, rodents exposed to stressors (eg, chronic social defeat) can also be classified into different phenotypes: the susceptible ones, which present behavioral changes related to anxiety and depression and decrease social interaction; and the resilient ones, which do not develop such maladaptive changes.In this context of the functional lateralization of the mPFC, the aim of the present study is to investigate behavioral changes related to anxiety (e.g., in the elevated plus maze test) and depression (e.g., forced swimming and sucrose consumption tests), as well as molecular changes (via immunohistochemistry for Fos family proteins in double labeling with the Calcium / calmodulin dependent protein kinase, member of the intracellular signaling cascade underlying the activation of NMDA glutamatergic receptors) involved in the expression of resilient and susceptible phenotypes to social defeat stress in mice. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANTOS-COSTA, NATHALIA; BAPTISTA-DE-SOUZA, DANIELA; CANTO-DE-SOUZA, LUCAS; DA COSTA, VINICIUS FRESCA; NUNES-DE-SOUZA, RICARDO LUIZ. Glutamatergic Neurotransmission Controls the Functional Lateralization of the mPFC in the Modulation of Anxiety Induced by Social Defeat Stress in Male Mice. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 15, AUG 23 2021. (17/25409-0, 16/24568-4, 16/08665-0)

VICTORIANO, GABRIEL; SANTOS-COSTA, NATHALIA; MASCARENHAS, DIEGO CARDOZO; NUNES-DE-SOUZA, RICARDO LUIZ. Inhibition of the left medial prefrontal cortex (mPFC) prolongs the social defeat-induced anxiogenesis in mice: Attenuation by NMDA receptor blockade in the right mPFC. Behavioural Brain Research, v. 378, JAN 27 2020. (16/24568-4, 17/25409-0, 13/01283-6)