The role of mitochondrial NAD(P)+ transhydrogenase in monoaminergic neurotransmission and neurodegeneration in mice

• Grant number: 20/05202-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2020
• End date: February 28, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Roger Frigério Castilho
• Grantee: Annelise Francisco
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/17728-8 - Mitochondrial function and dysfunction: implications for aging and associated diseases, AP.TEM

Abstract

Previous studies have shown that NAD(P)+ transhydrogenase (NNT) is relevant to maintenance of mitochondrial redox balance in mouse brain, especially under physiologically challenging conditions, such as after treatment with a high-fat diet. In this sense, this project aims at study the role of NNT activity in the development of age-related changes in the central nervous system using a mouse model. Changes in mitochondrial bioenergetics, oxidative damage and morphological changes related to aging in the brain of mice with and without functional NNT will be characterized. Besides, changes in neurotransmission and putative behavioral phenotypes in mice devoid of functional NNT will be evaluated. Methodological approaches will include behavioral assays, assessment of the bioenergetic and redox balance in isolated mitochondria, assessment of oxidative damage markers, immunoenzymatic assays and immunohistochemical and immunofluorescence analyzes in brain. (AU)

Scientific publications

(6)

(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)

NAVARRO, CLAUDIA D. C.; FRANCISCO, ANNELISE; FIGUEIRA, TIAGO R.; RONCHI, JULIANA A.; OLIVEIRA, HELENA C. F.; VERCESI, ANIBAL E.; CASTILHO, ROGER F.. ichloroacetate reactivates pyruvate-supported peroxide removal by liver mitochondria and prevents NAFLD aggravation in NAD(P)(+) transhydrogenase-null mice consuming a high-fat die. European Journal of Pharmacology, v. 917, FEB 15 2022. (20/05202-4, 19/20855-7, 17/17728-8)

FRANCISCO, ANNELISE; ENGEL, DAIANE F.; FIGUEIRA, TIAGO R.; ROGERIO, FABIO; DE BEM, ANDREZA F.; CASTILHO, ROGER F.. Mitochondrial NAD(P)(+) Transhydrogenase is Unevenly Distributed in Different Brain Regions, and its Loss Causes Depressive-like Behavior and Motor Dysfunction in Mice. Neuroscience, v. 440, p. 210-229, AUG 1 2020. (17/17728-8, 15/22063-0, 18/01360-4, 20/05202-4)

BICEGO, RAFAELA; FRANCISCO, ANNELISE; RUAS, JULIANA S.; SIQUEIRA-SANTOS, EDILENE S.; CASTILHO, ROGER F.. Undesirable effects of chemical inhibitors of NAD(P)(+) transhydrogenase on mitochondrial respiratory function. Archives of Biochemistry and Biophysics, v. 692, p. 12-pg., 2020-10-15. (17/17728-8, 20/05202-4, 15/22063-0)

FRANCISCO, ANNELISE; FIGUEIRA, TIAGO REZENDE; CASTILHO, ROGER FRIGERIO. Mitochondrial NAD(P)(+) Transhydrogenase: From Molecular Features to Physiology and Disease. Antioxidants & Redox Signaling, AUG 2021. (17/17728-8, 20/05202-4)

FIGUEIRA, TIAGO R.; FRANCISCO, ANNELISE; RONCHI, JULIANA A.; DOS SANTOS, GUILHERME R. R. M.; DOS SANTOS, WILLIAM; TREBERG, JASON R.; CASTILHO, ROGER F.. NADPH supply and the contribution of NAD(P)(+) transhydrogenase (NNT) to H2O2 balance in skeletal muscle mitochondria. Archives of Biochemistry and Biophysics, v. 707, AUG 15 2021. (11/51800-1, 20/05202-4, 18/04559-6, 17/17728-8)

SILVA, ELLEN A. A.; DALLA COSTA, ANA P. P.; RUAS, JULIANA S. S.; SIQUEIRA-SANTOS, EDILENE S. S.; FRANCISCO, ANNELISE; CASTILHO, ROGER F. F.. Proliferating Astrocytes in Primary Culture Do Not Depend upon Mitochondrial Respiratory Complex I Activity or Oxidative Phosphorylation. CELLS, v. 12, n. 5, p. 17-pg., 2023-03-01. (17/17728-8, 20/05202-4)