INTR10

Authors:

Cavaliere F 1; Alberdi E 1; Matute C 1

Institutions:

1 Neurotek-UPV/EHU

Title of abstract : Block of P2X receptors reduces delay time between cortical damage and activation of neurogenesis in a 3D model of in vitro ischemia

Abstract text:

Background. Adult neurogenesis occurs in different regions of adult CNS under physiological and pathological conditions. Neurogenesis induced in SVZ by ischemia is basically described by:
• Enhanced progenitor proliferation
• Migration of proliferating cells into the damaged area
• Differentiation and integration into pre-existing neuronal circuitries
Local environment is the main modulator of induced neurogenesis. Extracellular released ATP is among the factors contributing to impede regular activation of neurogenesis. This is suggested by several evidences:
• Massive release of ATP following metabolism impairment is neurotoxic
• Calcium signalling, even from P2X-Y receptors regulates proliferation and differentiation of different stem cells
• Purinergic signalling regulates neural progenitor’s expansion and neurogenesis under physiological conditions
• Ectonucleotidases are functionally expressed on progenitor cells
The Model. In this work we use rat organotypic culture from cortex-SVZ-striatum to model neuroblasts activity. The presence of SVZ in the slices, and its connectivity to the striatum and cortex through the corpus callosum, confers a 3D structure allowing studying the mechanisms of stem cell proliferation and neurogenesis and its further modulation by ischemic environment
Results. The results obtained here demonstrate that
• Neurogenesis activation induced by in vitro ischemia is delayed due to the negative modulation of ischemic environment
• Neurogenesis activation is negatively modulated by extracellular ATP
• Block of purinergic P2X receptors boosts early activation of neurogenesis and sustains rapid neuroblasts migration into the damaged cortex
• Early neuroblasts migration induced by block of P2X receptors does occur without cell proliferation

This entry was posted on Tuesday, July 15th, 2008 at 15:43 and is filed under Repair mechanisms and stroke, all. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.