The role of corticosterone in mitochondrial function and dynamics in mice primary hippocampal neuronal cell cultures: the involvement of Mitofusin 2

• Grant number: 20/11250-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2020
• Effective date (End): April 30, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Nilton Barreto dos Santos
• Grantee: Luiza Helena Halas Covre
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Stress-related mood disorders have a significant impact on health and economy worldwide. In addition to being related to various disturbances in different neurotransmitter systems, stress also seems to be an essential modulator in depression. Patients with major depressive disorder, the most severe depressive disorder, show augmented plasmatic cortisol, and adrenal activity. Glucocorticoids, cortisol in humans and corticosterone (CORT) in rodents, are steroid hormones that mediate the stress response, exerting their systemic effects, including anti-inflammatory and electrolytic control, by activating receptors for glucocorticoids (GRs) and mineralocorticoids (MRs), respectively. However, during prolonged stress, their concentration increase is associated with deleterious and cytotoxic effects in the encephalon, hippocampus, and prefrontal cortex (PFC), resulting in cell death. Some clinical findings in depressive patients, i.e. the hippocampus and PFC atrophy and the amygdala hyperactivity, are also observed in some mitochondrial disorders. In the central nervous system, the optimal mitochondria function is vital to brain homeostasis. Stress and CORT treatment are also associated with modifications in mitochondrial and autosomal gene expression, inducing an increase of oxidative stress, possible calcium homeostasis, and mitochondrial dynamics (mitochondrial fusion and fission) changes, essential to modulate mitochondrial size and number and to allow mitochondria to adapt in different physiological situations. Thus, the goal of this project is to elucidate the mitochondrial effects of CORT in C57BL/6 (P1-P4) newborn mice primary hippocampal neuronal cell cultures, especially on the mitochondrial fusion and fission, as well as to assess the effect of CORT on the mitochondrial calcium homeostasis.