Age-related mitochondrial metabolism and its relationship with neurogenesis in an animal model of schizophrenia

• Grant number: 18/08399-3
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2019
• End date: January 31, 2021
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Agreement: University of Victoria
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Tatiana Rosado Rosenstock
• Grantee: Tatiana Rosado Rosenstock
• Principal researcher abroad: Joana Maria Amaral Campos Gil Mohapel
• Institution abroad: University of Victoria (UVic), Canada
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/02041-1 - The role of lysine(K)-deacetylases on mitochondrial disorders's neuroprotection: perspectives of epigenetic therapy for amyotrophic lateral sclerosis and schizophrenia, AP.JP

Abstract

Neuroprogression is one of several theories that have been proposed to explain the neuropathological features of Schizophrenia (SHZ). According to it, cellular changes, such as modifications in cell proliferation, neuronal migration and differentiation, as well as alterations in synapse formation are increased by sequential psychotic episodes and aggravated in the absence of medical intervention, leading to degenerative processes (cell death). Since both synaptic transmission and brain plasticity (i.e., neurogenesis) rely on ATP production, maintenance of mitochondrial metabolism is essential, both for neuronal regulation and survival. Given this, the goal of the current project is to concomitantly evaluate mitochondrial, neuronal, and behavioral alterations in an animal model of SHZ, the spontaneous hypertensive (SHR) rat model. For all experiments, SHR rats will be used at 2, 4, 6 and 9 months of age, which will allow the detection of metabolic and neuroplastic alterations that may precede the onset of schizophrenia-like symptoms which, in this animal model, are observed at around 4 months of age. Thus, the results of this study will help elucidating the cellular metabolic alterations that occur in SHZ and how these correlate with changes in neuronal plasticity and neurodegeneration and ultimately the progression of SHZ. In addition, the findings from this project may aid in the identification of a biomarker that may be used, in conjunction with clinical indexes, to monitor the course of this psychiatric disorder and its response to treatment. (AU)