NCLX in astrocytic function: metabolism and neuronal homeostasis

• Grant number: 19/22178-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 01, 2020
• End date: January 29, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Alicia Juliana Kowaltowski
• Grantee: João Victor Cabral Costa
• Supervisor: Juan P. Bolaños
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Universidad de Salamanca (USAL), Spain
• Associated to the scholarship: 17/14713-0 - Mitochondrial Ca2+ Handling in the Central Nervous System and Energy Metabolism Regulation, BP.DR

Abstract

Ca2+ is an ion of seminal importance not only in the context of excitotoxicity, but also physiologically, participating in many key processes in the central nervous system, including dendritic development, synaptogenesis, neurotransmitter release, and synaptic plasticity. Ca2+ ions can also act as a marker for activity regarding energetic demands, and are an important regulator of metabolism, coupling metabolic needs dictated by cellular activity with ATP production. Mitochondria have a well-developed Ca2+ transport system. Mitochondrial Ca2+ efflux is physiologically carried out by the mitochondrial Na2+/Ca2+ exchanger (NCLX), which also has a potential role in the regulation of synaptic transmission and plasticity. NCLX was recently associated with pathological mechanisms of Parkinson's disease models, and its expression was shown to be decreased in - and inversely correlated with the prognosis of - Alzheimer's disease. In astrocytes, an important glial cell type with a complex and a highly arborized structure, NCLX influences the shaping of cytosolic Ca2+ signaling, modulating proliferation and glutamate release. The function of NCLX in cellular homeostasis, however, is still mainly unexplored by the literature. This project aims to investigate the role of NCLX on astrocytic function in vivo and in vitro. (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)

CABRAL-COSTA, JOAO VICTOR; KOWALTOWSKI, ALICIA J.. Mitochondrial Ca2+ handling as a cell signaling hub: lessons from astrocyte function. ESSAYS IN BIOCHEMISTRY, v. 67, n. 1, p. 13-pg., 2023-03-01. (13/07937-8, 20/06970-5, 17/14713-0, 19/22178-2)

CABRAL-COSTA, JOAO VICTOR; VICENTE-GUTIERREZ, CARLOS; AGULLA, JESUS; LAPRESA, REBECA; ELROD, JOHN W.; ALMEIDA, ANGELES; BOLANOS, JUAN P.; KOWALTOWSKI, ALICIA J.. Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance. Journal of Neurochemistry, v. N/A, p. 15-pg., 2023-01-09. (13/07937-8, 17/14713-0, 20/06970-5, 19/22178-2)

PEREIRA JR, O. R.; RAMOS, V. M.; CABRAL-COSTA, J. V.; KOWALTOWSKI, A. J.. Changes in mitochondrial morphology modulate LPS-induced loss of calcium homeostasis in BV-2 microglial cells. Journal of Bioenergetics and Biomembranes, v. 53, n. 2, p. 109-118, APR 2021. (19/18402-4, 19/22178-2, 20/06970-5, 17/14713-0, 18/21487-9, 13/07937-8)