Neuroprotection by R(-)-deprenyl and N-2-hexyl-N-methylpropargylamine on DSP-4, a neurotoxin, induced degeneration of noradrenergic neurons in the rat locus coeruleus.
N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a neurotoxin and capable of selectively depleting noradrenergic axons and subsequently causing lesions of locus coeruleus (LC) noradrenergic neurons in the rat. R(-)-deprenyl and N-(2-hexyl)-N-methylpropargylamine (2-HxMP) have been previously shown to be quite effective in protecting NA nerve fibers in different brain tissues against DSP-4. The present report reveals the neuroprotective effect of these drugs on the LC noradrenergic cell bodies using a histochemical method. Neurons were quantitatively assessed using Nissl-stained sections. DSP-4 induced a 34% loss of LC perikarya neurons 3 months after a single systemic administration in comparison to control animals. Approximately 90% and 88% of neurons in the same regions survived against DSP-4 induced insult following multiple injections of R(-)-deprenyl and 2-HxMP, respectively. The neuroprotective effect towards the LC neurons against DSP-4 is probably due to prevention of retrograde degeneration of NA axons.
Zhang
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X
Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.
Zuo
D M
DM
Yu
P H
PH
D018663:Adrenergic Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D001596:Benzylamines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008125:Locus Coeruleus / Q000166:cytology* / Q000187:drug effects; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000502:physiology*; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology*
D018663:Adrenergic Agents; D001596:Benzylamines; D011437:Propylamines; C094098:N-2-hexyl-N-methylpropargylamine; D012642:Selegiline; C012102:DSP 4; D009638:Norepinephrine