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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
Author(s) -
Zhang X.,
Zuo D.M.,
Davis B.A.,
Boulton A.A.,
Yu P.H.
Publication year - 1996
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19960215)43:4<482::aid-jnr9>3.0.co;2-b
Subject(s) - locus coeruleus , neuroprotection , neurotoxicity , neurotoxin , hippocampus , chemistry , selegiline , neuroscience , dopamine , norepinephrine , rotenone , thalamus , biology , medicine , pharmacology , endocrinology , biochemistry , central nervous system , parkinson's disease , toxicity , mitochondrion , disease
DSP‐4 [ N ‐(2‐chloroethyl)‐N‐ethyl‐2‐bromobenzyl‐amine] 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‐β‐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. © 1996 Wiley‐Liss, Inc.