IN-VIVO EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN CEREBELLAR NEURONS

In the CNS, nitric oxide (NO) functions as both neuromodulator and neu rotoxic agent. In vivo neuronal expression of NO synthase (NOS) has be en attributed to constitutive NOS-both the neuronal and the endothelia l types. The other class of NOS-the inducible NOS (iNOS)-is known to m ediate toxic effects of NO in various tissues. In this study, we show for the first time that direct intracerebellar injection of endotoxin and cytokine (lipopolysaccharide and interferon-gamma) induced in vivo neuronal expression of the iNOS gene, as demonstrated by fluorescent in situ hybridization and immunohistochemical staining analyzed by con focal laser-scanning microscopy. This raises the possibility that neur onal iNOS might contribute significantly to the vulnerability of the b rain to various insults.