NOS EXPRESSION IN NIGRAL CELLS AFTER EXCITOTOXIC AND NON-EXCITOTOXIC LESION OF THE PENDUNCULOPONTINE TEGMENTAL NUCLEUS

The substantia nigra (SN) receives afferents from cholinergic neurons of the pedunculopontine tegmental nucleus (PPTg), a neuronal populatio n that shows high levels of nitric oxide synthase (NOS), the enzyme re sponsible for the synthesis of nitric oxide. We have investigated the effects of the injection in PPTg of two neurotoxins, kainic acid (an e xcitotoxic neurotoxin), and ethylcholine mustard azirinium ion (AF64A, a non-excitotoxic neurotoxin), upon the SN cells of the rat, by using choline acetyltransferase (ChaT) immunohistochemistry as a marker of cholinergic neurons, and nicotinamide adenine dinucleotide phosphate d iaphorase (NADPHd) histochemistry and NOS immunohistochemistry as mark ers of nitric oxide-producing neurons. Our results show that in normal rats, the SN contains two populations of NOS-positive neurons: large cholinergic neurons of PPTg that invade the caudal region of the SN, a nd small elongated neurons lying in the SN pars compacta. After ipsila teral PPTg lesion, another population of nigral cells, constituted by medium sized neurons, became NADPHD/NOS-pososive, This was much more e vident in AF64A-injected rats, in which many medium sized neurons show ed enzymatic activity and normal morphological features, at least duri ng the 90 days after injection. Kainic acid-injected rats, in contrast , showed nigral cell degeneration, an effect not found in AF64A materi al, and only a few NOS-positive neurons. NADPHd/NOS activity was never present in degenerating neurons. These findings suggest that inductio n of NOS activity is not involved in nigral cell degeneration, and tha t nitric oxide could have a protective rather than a neurotoxic role. The possible role of nitric oxide in the pathogenesis of Parkinson's d isease is discussed.