The endothelinergic system in adult neurogenesis

CASTAÑEDA M; LOPEZ VICCHI M; VILLAR MJ; SUBURO AM

Washington DC

Congreso; Society for Neuroscience Meeting 2008; 2008

Society for Neuroscience

The endothelinergic family includes at least three peptides (ET-1, ET-2, and ET-3) and two receptors (ETR-A and ETR-B). We have previously shown that the subventricular zone (SVZ) of mice contains ET(+) and ETR-B(+) cells. Since they also express Glial Fibrillary Acidic Protein (GFAP), subventricular endothelinergic cells might likely be neural precursor cells (NPCs).To test this hypothesis, we evaluated changes of endothelinergic cells under conditions stimulating growth and migration of NPCs. In addition, we assayed co-localization of endothelinergic molecules with putative NPC markers.Male C57Bl/6 mice (6-8 weeks old) were subjected to small devascularizing lesions of the motor-sensory cortex. Devascularized mice and sham-operated controls were euthatanized 5 days after surgery. Distribution of endothelinergic markers was evaluated by an immunoenzymatic procedure. Double and triple immunofluorescence confocal microscopy was used to study co-localization of ET and ETR-B with Prominin-1 (PROM) and nestin (NES).In control brains, ET(+) and ETR-B(+) were mainly found in the SVZ. A few cells were also present in the corpus callosum (CC) and cingulum (cg). After devascularization, endothelinergic cells and processes strikingly increased in those areas. In addition, they also appeared in the rostral migratory stream (RMS) and around the devascularized area. Changes of endothelinergic cells numbers and distribution paralleled similar changes of NPC markers.Co-localization experiments demonstrated that PROM was always present in endothelinergic cells, both in control and devascularized animals. NES labeling only appeared in devascularized animals. Under these conditions, triple labeled cells (ET or ETR-B with PROM and NES) were often found in the SVZ and RMS. NES increased and PROM decreased in the vicinity of the cortical lesion and ET/NES(+) cells predominated in the periphery of the lesion. The lesion core showed low levels of endothelinergic markers, and this region was mainly occupied by NES(+) cells. Autocrine endothelinergic stimulation could perhaps be involved in the regulation of adult murine NPCs. The system would remain active in more mature neuronal precursors expressing NES and probably disappears in more mature stages. Further studies are required to understand the role of endothelinergic molecules in adult neurogenesis.