Xavier F Figueroa
Pontificia Universidad Católica de Chile, Chile
Scientific Tracks Abstracts: Neurochem Neuropharm
Brain function depends on the coordination of neuronal activity and cerebral blood flow by a signalling mechanism known as neurovascular coupling. Neurotransmitters released during an increase in synaptic activity (e.g. glutamate) initiate a Ca2+ signalling in astrocytes, which activates the release of vasoactive factors from astrocytic endfeet to parenchymal arterioles. Then, changes in neuronal activity are coupled to local blood flow through regulation of arteriolar diameter. Although NO is one of the most important signalling molecules in vascular physiology, its participation in neurovascular coupling is controversial. However, astrocytes express the Ca2+-dependent NO-synthetizing enzymes eNOS and nNOS and NO modulate the activity of channels formed by connexins (gap junction channels and hemichannels) or pannexins, which coordinate the neurovascular coupling-associated astrocyte signalling. The participation of NO in the neurovascular coupling initiated by metabotropic glutamate receptor (mGluR) stimulation was assessed in primary cultures of astrocytes and rat brain slices. NO production, vasomotor response of brain cortex arterioles, activity of connexin hemichannels and pannexin channels, changes in [Ca2+]i and ATP release were evaluated. The results indicate that NO, but unexpectedly, also Ca2+ homeostasis modulator 1 (CALHM1) channels, are essential for the astrocyte signalling that mediates neurovascular coupling. Stimulation of astrocytes mGluRs leads to NO-mediated activation of CALHM1 channels by S-nitrosylation, which evokes ATP release. The subsequent ATP-dependent purinergic receptor stimulation induces the opening of Cx43 hemichannels and Panx-1 channels, which contributes to the astrocytic Ca2+ signalling. These findings may provide clues to the design of new therapeutic strategies for the treatment of neurodegenerative diseases.
Xavier F Figueroa has completed his PhD from Pontificial Catholic University of Chile and Post-doctoral studies from University of Virginia, Cardiovascular Research Center. Currently, he is Associate Professor at Pontificial Catholic University of Chile and is the Director of the laboratory of Vascular Biology at the Department of Physiology. He has published more than 30 papers in reputed peer-review journals, several of which have been highly cited. His laboratory combines cellular approaches with studies in intact and in vivo preparations to study the mechanisms involved in the control of microvascular function in peripheral tissues and in the brain.
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