Morphological bases for a role of nitric oxide in adult neurogenesis

The subventricular zone (SVZ) of the adult mouse brain retains the capacity to generate new neurons from stem cells. The neuronal precursors migrate tangentially along the rostral migratory stream (RMS) towards the olfactory bulb, where they differentiate as periglomerular and granular interneurons. In this study, we have investigated whether nitric oxide (NO), a signaling molecule in the nervous system with a role in embryonic neurogenesis, may be produced in the proximity of the progenitor cells in the adult brain, as a prerequisite to proposing a functional role for NO in adult neurogenesis. Proliferating and immature precursor cells were identified by immunohistochemistry for bromo-deoxyuridine (BrdU) and PSA-NCAM, respectively, and nitrergic neurons by either NADPH-diaphorase staining or immunohistochemical detection of neuronal NO synthase (NOS I). Nitrergic neurons with long varicose processes were found in the SVZ, intermingled with chains of cells expressing PSA-NCAM or containing BrdU. Neurons with similar characteristics surrounded the RMS all along its caudo-rostral extension as far as the core of the olfactory bulb. No expression of NOS I by precursor cells was detected either in the proliferation or in the migration zones. Within the olfactory bulb, many small cells in the granular layer and around the glomeruli expressed either PSA-NCAM or NOS I and, in some cases, both markers. Colocalization was also found in a few isolated cells at a certain distance from the neurogenesis areas. The anatomical disposition shown indicates that NO may be released close enough to the neuronal progenitors to allow a functional influence of this messenger in adult neurogenesis.