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-bromobenzyl amine] is a potent neur otoxin highly selective to the locus coeruleus noradrenaline (NA) syst em, Previous biochemical studies have shown that the monoamine oxidase -B (MAO-B) inhibitors, R(-)-deprenyl and (+/-)2-HxMP [N-(2-hexyl)-N-me thylpropargylamine], 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-hydroxylas e immunohistochemical and image analysis methods, we have shown that 9 2% and 84% of NA nerve fibers in the rat hippocampus are spared from D SP-4 neurotoxicity by a single pretreatment dose of either R(-)-depren yl 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 morphol ogical evidence demonstrating that R(-)-deprenyl and (+/-)2-HxMP can i ndeed protect noradrenergic axons of locus coeruleus origin against DS P-4 neurotoxicity. (C) 1996 Wiley-Liss, Inc.