Monoamine oxidase B inhibitor selegiline protects young and aged rat peripheral sympathetic neurons against 6-hydroxydopamine-induced neurotoxicity.

Abstract

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 by neurotoxins such as MPTP, DSP-4 and AF64A in animal studies. In addition, the protective action is not limited to catecholaminergic cells, as selegiline can also minimize the loss of developing motoneurons after axotomy. The aim of this study was to determine whether selegiline can protect peripheral catecholaminergic neurons against the neurotoxic effect of 6-OHDA. This kind of protective effect against 6-OHDA neurotoxicity has not been reported before. Wistar albino male rats aged 4 or 24 months were treated with selegiline or saline solution 1 h before 6-OHDA injection. At 2 weeks after the 6-OHDA injection, the superior cervical ganglia (SCG) and submandibular glands (SMG) were studied using catecholamine histofluorescence and immunohistochemistry for tyrosine hydroxylase (TH). The number of TH-positive cells in the SCG and the length and number of adrenergic nerve fibers in the SMG were quantified. Our findings showed that 6-OHDA caused a reduction of TH immunoreactivity and catecholamine histofluorescence in neuronal somata, as well as a decrease in the number and length of adrenergic nerve fibers in the submandibular gland. Selegiline pretreatment protected SCG neurons and their postganglionic nerve fibers in SMG against these changes in a dose-dependent manner. The mechanism through which selegiline exerts its neuroprotective effect is as yet unknown.