NCLX in astrocytic function: metabolism and neuronal homeostasis

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)