Destruction of locus coeruleus neuronal perikarya after injection of anti-dopamine-B-hydroxylase immunotoxin into the olfactory bulb of the rat.
Saporin, a ribosome-inactivating protein, was coupled to a monoclonal antibody to dopamine-B-hydroxylase (DBH) and injected unilaterally into the olfactory bulb of rats. After 4-13 days survival, the rat brain was processed histologically and the locus coerulei (LC) examined with Nissl and anti-DBH staining. There were degenerating dendrites in surviving LC neurons on the side ipsilateral to the immunotoxin-injected olfactory bulb. The number of Nissl-positive LC neurons in a transverse section through the caudal one third of the LC was reduced from 116+/-10 to 50+/-8 neurons (P < 0.01, n = 7) and the number of DBH-positive neurons in the more rostral LC sections was reduced from 13+/-2 to 5+/-1 (P < 0.05, n = 4). Our results indicate that it is possible to lesion LC neurons via retrograde intraaxonal transport of saporin-anti-DBH immunotoxin from the olfactory bulb.
Blessing
W W
WW
Department of Physiology and Medicine, Centre for Neuroscience, Flinders University Medical Centre, SA, Australia. w.w.blessing@flinders.edu.au
Lappi
D A
DA
Wiley
R G
RG
D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D004299:Dopamine beta-Hydroxylase / Q000276:immunology*; D000922:Immunotoxins / Q000493:pharmacokinetics*; D008125:Locus Coeruleus / Q000473:pathology*; D008297:Male; D008845:Microinjections; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism; D009434:Neural Pathways; D009562:Nissl Bodies / Q000737:chemistry / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D011916:Rats, Inbred F344; D012270:Ribosomes / Q000737:chemistry / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D000922:Immunotoxins; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine