Immunohistochemical evidence of neuroprotection by R(-)-deprenyl and N-(2-hexyl)-N-methylpropargylamine on DSP-4-induced degeneration of rat brain noradrenergic axons and terminals.

DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] is a potent neurotoxin highly selective to the locus coeruleus noradrenaline (NA) system. Previous biochemical studies have shown that the monoamine oxidase-B (MAO-B) inhibitors, R(-)-deprenyl and (+/-)2-HxMP [N-(2-hexyl)-N-methylpropargylamine], are able to prevent DSP-4 induced NA depletion in the mouse hippocampus. It is not quite certain, however, whether this actually represents neuroprotection of NA axons or a metabolic effect due to inhibition of MAO activity. Employing dopamine-beta-hydroxylase immunohistochemical and image analysis methods, we have shown that 92% and 84% of NA nerve fibers in the rat hippocampus are spared from DSP-4 neurotoxicity by a single pretreatment dose of either R(-)-deprenyl or (+/-)2-HxMP respectively. Similar neuroprotective effects of R(-)-deprenyl and (+/-)2-HxMP were also observed in the cerebral cortex, thalamus, amygdaloid complex and cerebellum. This is the first morphological evidence demonstrating that R(-)-deprenyl and (+/-)2-HxMP can indeed protect noradrenergic axons of locus coeruleus origin against DSP-4 neurotoxicity.