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

✍ Scribed by X. Zhang; D.-M. Zuo; B.A. Davis; A.A. Boulton; P.H. Yu

• Book ID: 102652157
• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 964 KB
• Volume: 43
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19960215)43:4<482::aid-jnr9>3.0.co;2-b

✦ Synopsis

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

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 MA0 activity. Employing dopamine-P-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.