Role of caloric restriction in the brain excitotoxicity

• Grant number: 12/51288-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2013
• End date: April 30, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Alicia Juliana Kowaltowski
• Grantee: Ignacio Amigo de La Huerga
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Caloric restriction has been shown to increase lifespan in a wide number of species, as well as to prevent the onset of several age-related diseases. In brain, the use of drugs that mimic some of the effects of caloric restriction has been shown to be protective against different morbid conditions, such as ischemia/reperfusion injury, Alzheimer's and Parkinson's diseases. However, the influence of caloric restriction on the susceptibility of brain cells to excitotoxicity has only been superficially studied, despite being tightly related to most cerebral pathological situations, including those mentioned above. The few studies that have addressed the issue show that caloric restriction reduces cell death induced by kainic acid in rodents, albeit no specific mechanisms were investigated. In this project, we propose to study the effects of caloric restriction in brain in response to excitotoxic stimuli and to unravel the molecular mechanisms and subcellular processes that underlie them. We present an approach that combines both in vivo and in vitro experiments, and that spans a wide number of techniques to deal with different aspects of the excitotoxic effects on neuronal cells. We believe that obtaining new insights into how caloric restriction exerts its effects in the brain can be of great importance, both to further understand how neurological disorders take place and to identify molecular targets for neuroprotection. (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)

AMIGO, IGNACIO; MENEZES-FILHO, SERGIO LUIZ; LUEVANO-MARTINEZ, LUIS ALBERTO; CHAUSSE, BRUNO; KOWALTOWSKI, ALICIA J.. Caloric restriction increases brain mitochondrial calcium retention capacity and protects against excitotoxicity. AGING CELL, v. 16, n. 1, p. 73-81, FEB 2017. (10/51906-1, 12/51288-1)

RUAS, JULIANA S.; SIQUEIRA-SANTOS, EDILENE S.; AMIGO, IGNACIO; RODRIGUES-SILVA, ERIKA; KOWALTOWSKI, ALICIA J.; CASTILHO, ROGER F.. Underestimation of the Maximal Capacity of the Mitochondrial Electron Transport System in Oligomycin-Treated Cells. PLoS One, v. 11, n. 3, MAR 7 2016. (12/51288-1, 10/51906-1, 11/50400-0, 13/07937-8)