MONOAMINE-OXIDASE-B INHIBITOR SELEGILINE PROTECTS YOUNG AND AGED RAT PERIPHERAL SYMPATHETIC NEURONS AGAINST 6-HYDROXYDOPAMINE-INDUCED NEUROTOXICITY

Selegiline is a selective and irreversible monoamine B inhibitor with the capacity to increase the level of several antioxidative enzymes in rat brain. It can protect adrenergic neurons against injury induced b y neurotoxins such as MPTP, DSP-4 and AF64A in animal studies. In addi tion, the protective action is not limited to catecholaminergic cells, as selegiline can also minimize the loss of developing motoneurons af ter axotomy. The aim of this study was to determine whether selegiline can protect peripheral catecholaminergic neurons against the neurotox ic effect of 6-OHDA. This kind of protective effect against 6-OHDA neu rotoxicity has not been reported before. Wistar albino male rats aged 4 or 24 months were treated with selegiline or saline solution 1 h bef ore 6-OHDA injection. At 2 weeks after the 6-OHDA injection, the super ior cervical ganglia (SCG) and submandibular glands (SMG) were studied using catecholamine histofluorescence and immunohistochemistry for ty rosine hydroxylase (TH). The number of TH-positive cells in the SCG an d the length and number of adrenergic nerve fibers in the SMG were qua ntified. Our findings showed that 6-OHDA caused a reduction of TH immu noreactivity and catecholamine histofluorescence in neuronal somata, a s well as a decrease in the number and length of adrenergic nerve fibe rs in the submandibular gland. Selegiline pretreatment protected SCG n eurons and their postganglionic nerve fibers in SMG against these chan ges in a dose-dependent manner. The mechanism through which selegiline exerts its neuroprotective effect is as yet unknown.