Endothelin in the subventricular zone of mice

CASTAÑEDA M; LOPEZ VICCHI M; SUBURO AM

Magdeburg

Congreso; 5th International Symposium on Neuroprotection and Neurorepair (Cerebral Ischemia and Stroke); 2008

Endothelin isoforms ET-1, -2, and -3, signal through receptors ETR-A and ETR-B. ET-1, the best known isoform, is a potent mitogen in many cells, including astrocytes. Since adult neural precursor cells (NPCs) share phenotypical characteristics with astroglia and express glial fibrillary acidic protein (GFAP), we studied endothelinergic molecules in the subventricular zone (SVZ). Cells from this neurogenic niche, located along the lateral wall of the lateral ventricle (LWLV), proliferate and migrate towards the olfactory bulb along the rostral migratory stream (RMS).Methods:Male C57Bl/6 mice (6-8 weeks old) were euthanatized and fixed by paraformaldehyde perfusion. Brains were cryosectioned and immunolabeled with antibodies recognizing ET-1, ET1+ET2+ET3 (pan-ET), ETR-A, ETR-B, GFAP and prominin-1, an NPC marker. Antibody binding was detected by immunoenzymatic or immunofluorescence procedures. Granulocyte-Colony Stimulating Factor (G-CSF) or devascularization of cortical areas M1, M2 and S1 were used to enhance NPC proliferation and migration. Experimental groups and their corresponding controls were fixed 5 days after surgery or G-CSF treatment.Results:In normal mice, ET-1 and pan-ET immunoreactivities were found in cells and processes along the LWLV and the RMS. ETs also appeared in a few cells within the corpus callosum (CC), dorsal to the RMS. The SVZ showed no ETR-A immunoreactivity, but exhibited low levels of ETR-B. ET-1 and ETR-B immunoreactivities increased after G-CSF treatment or ipsilateral devascularization. Under these conditions, the RMS enlarged laterally beneath the CC and included many cells expressing ET-1, pan-ET-1 and ETR-B immunoreactivities. Cells with the same immunoreactivities also increased within the CC, being most numerous at the cingulum. ETR-A was undetectable in these regions.Every levels of the SVZ and RMS showed co-localization of ET-1 and ETR-B with the NPC markers prominin-1 and GFAP.ConclusionsThe SVZ contained cells with ET and ETR-B immunoreactivities. Endothelinergic cells increased after neurogenesis activation, suggesting a relationship to NPC lineages. Co-localization of ET-1 and ETR-B with characteristic NPC markers supports this hypothesis. Endothelinerg signals could regulate proliferation, migration and differentiation of NPCs, and might also be important for repair of cortical injuries.