Expression of neuronal nitric oxide synthase/NADPH-diaphorase during olfactory deafferentation and regeneration

Neuronal nitric oxide synthase (nNOS) expression can be regulated under nat ural or experimental conditions. This work aims at elucidating whether the expression of nNOS or its related NADPH-diaphorase (ND) activity are modifi ed by manipulation of the normal inputs to neurons. We used the olfactory b ulbs from two mouse strains, BALE and CD1, because they show divergences in their synapse patterns, and these differences affect periglomerular cells, interneurons expressing tyrosine hydroxylase or nNOS/ND. The olfactory inp uts to these neurons can be disrupted by inhalation of methyl bromide. The effect of this gas on olfactory axons, as well as the synaptic features in both mouse strains, were studied using electron microscopy. The changes in expression were analysed qualitatively and quantitatively at different time s after lesion to nine topographical regions of the olfactory bulb. Methyl bromide inhalation induced a degeneration of olfactory axons in both strain s, but had different effects on the expression of nNOS/ND and tyrosine hydr oxylase. In BALB mice. where periglomerular cells do not receive direct inp uts from olfactory axons, no changes were detected in tyrosine hydroxylase or in ND expression. In CD1 periglomerular cells, where olfactory axons est ablish direct synapses, a significant down-regulation of both markers was o bserved. These changes were observed differentially across the olfactory bu lb, being more pronounced in rostral regions and more acute for ND than for tyrosine hydroxylase. Our results indicate that the synaptic inputs influe nce the expression of ND activity related to nNOS and that the activation o f the enzyme is more severely affected than its protein expression.