Regulació de la guanilil ciclasa soluble astroglial per agents inflamatoris. Mecanisme i implicacions funcionals

  • García Sánchez, Maria Carme Agustina (Principal Investigator)
  • Baltrons Soler, Maria Antonia (Researcher on contract)
  • Garcia Haro, Francisca (Researcher on contract)
  • Navarra, Michele (Investigator)

Project Details

Description

Soluble guanylyl cyclase (sGC) is the major physiological target for NO. In the CNS, cyclic GMP (c(GMP) can be formed by NO stimulation of sGC both in neurones and in astrocytes and it has been implicated in the regulation of synaptic plasticity, neural development, nociception and neuroendocrine secretion. There is abundant information in the literature about NO synthase type 2 (NOS-2) induction by inflammatory agents in CNS cells, in particular microglia and astroglia, both in culture and in animal models of inflammation and post-mortem tissue from patients with Multiple Sclerosis, Alzheimer's and Parkinson's diseases. In these situations, NO is abnormally elevated and has been implicated in neurotoxicity. In contrast, very little is known about the regulation of cGMP formation during neuroinflammation and there is contradictory information about its implication in neurotoxicity. In our lab, we have recently obtained evidence that treatment with bacterial endotoxin (LPS), proinflammatory cytokines (IL-1\beta, TNF-\alpha) and \beta-amiloid peptides decreases the capacity of rat brain astroglial cells to generate cGMP in response to NO as a result of decreased sGC expression. This could be a nechanism to prevent excess signalling via cGMP even when NO levels are elevated. We have also observed that IL-1\beta induces cGMP efflux from astroglial cells. In this project we propose to continue these studies with following objectives
StatusFinished
Effective start/end date28/12/0127/12/04

Funding

  • Ministerio de Ciencia y Tecnología: €117,497.86

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