In the central nervous system, nitric oxide (NO) has many functions, acting as an unconventional neuronal messenger and being synthesized on demand. It is generated by NO synthase (NOS), an enzyme expressed by discrete neuronal populations. After a brief critical evaluation of the histochemical methods used in the detection of NOS, and in particular of NOS-dependent NADPH diaphorase (NADPHd), this review will describe the localization of nNOS/NADPHd in the CNS of different species of both invertebrates and vertebrates, and during and after damage induced by experimental injuries. The aim is to demonstrate in situ NOS, and therefore the involvement of NO, in neural aspects of behaviour and development, and in degenerative and regenerative processes. We have considered the following CNS areas: (i) the ganglia of Helix aspersa (Gastropoda Pulmonata) during periods of activity and inactivity; (ii) the optic lobes of the medfly Ceratitis capitata (Diptera, Tephritidae), comparing two different strains, also during development; (iii) the cerebellum of Rana esculenta after unilateral transection of the eighth nerve; and (iv) the cerebellum of the rat during postnatal development, following treatment with the cytostatic cisplatin.
(i) In Helix aspersa, an increased number of NOS/NADPHd-positive neurons is observed in the cerebral ganglia during inactivity compared with the low number during activity; the buccal ganglia show an opposite trend. The data suggest that in the cerebral ganglia, which are the integration centre for several stimuli, the presence of NOS can be related to some forms of behaviour such as mating and feeding; moreover, NO may have a neuroprotective role in preventing degeneration when cerebral neurons suppress or reduce their activity. The buccal ganglia, on the other hand, are involved primarily in the regulation of feeding processes, which are totally suppressed during inactivity. The fact that buccal ganglia contain positive neurons during activity suggests an involvement of NO in feeding behaviour. (ii) The increase of NADPHd labelling from the pupal to the juvenile fly stage for both wild-type and white eye mutant medfly suggests that NO could be involved in the establishment of the retinal projection pattern, and in the formation and maintenance of synaptic connections. Moreover, the lower NADPHd labelling observed in the white eye optic lobes than in wild-type ones at all stages of development suggests that NOS and NADPHd variations may be responsible for, or linked to, an alteration to visual mechanisms that causes differences in visual response or discrimination in the white eye mutant. (iii) In the cerebellum of the frog Rana esculenta, increased expression of NADPHd/NOS is found after axotomy, with differences in the time course of the responses on the ipsilateral and contralateral sides to the lesion, that express the stages of vestibular compensation. On the basis of previously studied markers, it is proposed that the early induction or de novo synthesis of nNOS after neurectomy is linked to an early cytotoxic role of NO inducing degeneration of a fraction of the Purkinje neurons, while the persistent NOS labelling at late stages may be due to a neuroprotective role of NO in the restoration phase of the vestibular compensation process. (iv) In the postnatal cerebellar histogenesis of rat, the transient expression of NOS during Purkinje cell differentiation and the comparison between control and cisplatin-treated animals, in which decreased NOS/NADPHd labelling is found, demonstrates the trophic-regulatory role of this molecule in the crucial steps of cell differentiation concomitant with the normal development of cerebellar folia. This overview demonstrates the versatility and the differential role of NO, in simple and complex CNSs, that will be discussed in relation to other research on this almost ubiquitous signal molecule.
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