LOCALIZATION OF NITRIC-OXIDE SYNTHASE IN THE ADULT-RAT BRAIN

The distribution of the immunoreactivity to nitric oxide synthase has been examined from rostral to caudal areas of the rat central nervous system using light microscopy. Endogenous nitric oxide synthase was lo cated using a specific polyclonal antiserum, produced against affinity purified nitric oxide synthase from whole rat brain, following the av idin-biotin peroxidase procedure. Immunoreactive cell bodies and proce sses showed a widespread distribution in the brain. In the telencephal on, immunoreactive structures were distributed in all areas of the cer ebral cortex, the ventral endopiriform nucleus and claustrum, the main and accessory olfactory bulb, the anterior and posterior olfactory nu clei, the precommisural hippocampus, the taenia tecta, the nucleus acc umbens, the stria terminalis, the caudate putamen, the olfactory tuber cle and islands of Calleja, septum, globus pallidus and substantia inn ominata, hippocampus and amygdala. In the diencephalon, the immunoreac tivity was largely found in both the hypothalamus and thalamus. In the hypothalamus, immunoreactive cell bodies were characteristically loca ted in the perivascular-neurosecretory systems and mamillary bodies. I n addition, immunoreactive nerve fibres were detected in the median em inence of the infundibular stem. The mesencephalon showed nitric oxide synthase immunoreactivity in the ventral tegmental area, the interped uncular nucleus, the rostral linear nucleus of the raphe and the dorsa l raphe nucleus. Immunoreactive structures were also found in the nucl ei of the central grey, the peripeduncular nucleus and substantia nigr a pars lateralis, the geniculate nucleus and in the superior and infer ior colliculi. The pens displayed immunoreactive structures principall y in the pedunculopontine and laterodorsal tegmental nuclei, the ventr al tegmental nucleus, the reticulotegmental pontine nucleus, the parab rachial nucleus and locus coeruleus. In the medulla oblongata, immunor eactive neurons and processes were detected in the principal sensory t rigeminal nucleus, the trapezoid body, the raphe magnus, the pontine r eticular nuclei, the supragenual nucleus, the prepositus hypoglossal n ucleus, the medial and spinal vestibular nuclei, the dorsal cochlear n ucleus, the medullary reticular field, the nucleus of the solitary tra ct, the gracile and cuneate nuclei, the dorsal nucleus of the vagus ne rve and the oral, interpolar and caudal parts of the spinal trigeminal nucleus. In the cerebellum, the stellate and basket cells showed immu noreactivity, which was also seen in the basket terminal fibres of the Purkinje cell layer. Isolated immunoreactive Purkinje cells were foun d in the vermis and parafloccular regions of the cerebellum. In the gr anular layer of the cerebellum, the granular cells and glomeruli were also immunoreactive. Numerous positive varicose nerve fibres and occas ional neurons were also found in the lateral and interposed cerebellar nuclei. Immunoreactive processes were found close to and penetrating the ependymal cells of the ventricular walls, particularly the lateral ventricles. Immunoreactive cell bodies were also detected in the circ umventricular organs, including the subfornical organ and area postrem a. Cerebral blood vessels were largely surrounded by varicose immunore active neuronal processes forming dense networks. Our demonstration of the widespread distribution of the enzyme nitric oxide synthase in di verse nuclei of the rat brain generally confirms earlier histochemical studies and suggests that this enzyme may affect the function of vari ous neurotransmitter-specific systems. The possible implication of nit ric oxide synthase in the regulation of the cerebrospinal fluid system and of cerebral blood circulation is discussed.