Immune lesions of central noradrenergic neurons produced by antibodies to dopamine-beta-hydroxylase.
(1) Intraventricular injection of antibodies to dopamine-beta-hydroxylase (DBH) caused degeneration of central noradrenergic nerve terminals in rats and guinea-pigs. In rats it was necessary to infuse exogenous complement in the form of guinea-pig serum together with the anti-DBH, whereas in guinea-pigs the anti-DBH was effective on its own. Control animals were infused with equivalent amounts of non-immune serum and complement and showed no signs of degeneration other than in the region of the needle tract. (2) There was a loss of varicosities in most terminal fields of the noradrenergic projections and swollen distorted axons were seen in both ascending and descending noradrenergic pathways. Noradrenergic cell bodies in the locus coeruleus and subcoeruleus appeared unaffected. No histochemical changes were observed in dopaminergic neurons. (3) The ultrastructural changes in degenerating axons that were first identifided by fluorescence histochemistry included swelling, vacuolation, accumulation of dense cored vesicles, lysosome-like bodies and smooth membranous sacs. The surrounding neuropil appeared normal. (4) There was a significant depletion of noradrenaline in all regions of the rat brain ranging from 20% in the hypothalamus to 80% in the neocortex. Dopamine concentrations were unaffected. (5) These observations provide a new approach to the production of selective lesions in specific neurotransmitter pathways that could be extended to non-adrenergic neurones. They may also be useful as a model for the study of autoimmune diseases of the nervous system.
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D001369:Axons / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D003165:Complement System Proteins; D004298:Dopamine / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000276:immunology*; D006168:Guinea Pigs; D007031:Hypothalamus / Q000187:drug effects; D007276:Injections, Intraventricular; D008526:Medulla Oblongata / Q000187:drug effects; D008636:Mesencephalon / Q000187:drug effects; D008856:Microscopy, Fluorescence; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D011149:Pons / Q000187:drug effects; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects; D012154:Reticular Formation / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects
D000906:Antibodies; D011941:Receptors, Adrenergic; D003165:Complement System Proteins; D004299:Dopamine beta-Hydroxylase; D004298:Dopamine; D009638:Norepinephrine