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.
Zhang
X
X
Neuropsychiatry Research Unit, University of Saskatchewan, Saskatoon, Canada.
Zuo
D M
DM
Davis
B A
BA
Boulton
A A
AA
Yu
P H
PH
D000818:Animals; D001369:Axons / Q000737:chemistry / Q000187:drug effects*; D001596:Benzylamines / Q000037:antagonists & inhibitors; D007150:Immunohistochemistry; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000187:drug effects*; D009411:Nerve Endings / Q000737:chemistry / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000032:analysis; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012642:Selegiline / Q000494:pharmacology; D012680:Sensitivity and Specificity
D001596:Benzylamines; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011437:Propylamines; C094098:N-2-hexyl-N-methylpropargylamine; D012642:Selegiline; C012102:DSP 4; D009638:Norepinephrine