NITRIC OXIDE-MEDIATED CGMP SYNTHESIS IN OLIGODENDROCYTES IN THE DEVELOPING RAT-BRAIN

We investigated the nature of cGMP-synthesizing cells in the developin g rat forebrain using cGMP-immunocytochemistry in combination with in vitro incubation of brain slices. When brain slices of immature rats, aged between 1 and 4 weeks, were incubated with sodium nitroprusside ( SNP), a nitric oxide (NO) donor compound, in the presence of the phosp hodiesterase inhibitor isobutylmethylxanthine (IBMX), small round cell s with a few processes in and around the corpus callosum were visualiz ed with the cGMP-antibody. The morphology and the distribution of the cGMP-positive cells were consistent with the criteria for oligodendroc ytes. Furthermore, the cGMP-positive cells expressed 2'3'-cyclic nucle otide 3'-phosphodiesterase (CNPase) and gelsolin, which are marker pro teins for oligodendrocytes. Therefore, we concluded that the cGMP-posi tive cells were oligodendrocytes. A subpopulation of the oligodendrocy te was found to be cGMP-immunoreactive also when slices were incubated in the absence of SNP, Furthermore, incubation of the slice in the pr esence of L-NAME, an inhibitor of NO synthase, but in the absence of S NP abolished cGMP immunostaining. In addition, some populations of neu rons and astrocytes in restricted brain areas produced cGMP in respons e to the incubation with SNP as previously reported, whereas both ameb oid and ramified microglial cells did not respond to the treatment. At rial natriuretic peptide, a stimulator of particulate guanylyl cyclase , enhanced cGMP synthesis in astrocytes in some brain regions but not in oligodendrocytes. These findings indicate that oligodendrocytes in the immature rat brain express soluble guanylyl cyclase. No cGMP-posit ive oligodendrocytes were found in the mature rat brain, suggesting th at cGMP may mediate signals related to myelinogenesis in the rat brain . (C) 1997 Wiley-Liss, Inc.