An experimental model for the non-invasive trans-synaptic induction of nitric oxide synthase in Purkinje cells of the rat cerebellum

Nitric oxide synthase and its product nitric oxide are believed to be significantly involved in neuronal degeneration associated with various excitotoxic events and in some acute and chronic neuropathological disease states. The synchronous activation of inferior olive neurons by the drug harmaline is known to produce tremorogenic activity in rats via increased stimulation of the olivocerebellar system. Following subcutaneous or intraperitoneal injection (15, 30 or 60mg/kg) of harmaline and survival intervals of three days or more, NADPH-diaphorase histochemistry and nitric oxide synthase immunocytochemistry revealed nitric oxide synthase induction in Purkinje cells of the cerebellar vermis and paravermis, but not the lateral hemispheres. Double labeling with NADPH-diaphorase and calbindin revealed that induced Purkinje cells contain calbindin and that induced Purkinje cells are not necessarily associated with regions of Purkinje cell degeneration. The induction of nitric oxide synthase in a subpopulation of Purkinje cells may reflect a protective response of selected Purkinje cells to overstimulation of specific olivocerebellar projections. This is the first experimental model for the non-invasive induction of nitric oxide synthase in central nervous system neurons and as such may provide a useful tool for studying the induction of nitric oxide synthase associated with excitotoxic events.