Acetylcholinesterase immunolesioning: regional vulnerability of preganglionic sympathetic neurons in rat spinal cord.
Rats given antibodies against acetylcholinesterase (AChE) develop sympathetic dysfunction stemming from losses of preganglionic neurons in spinal cord. Central effects of AChE antibodies are surprising since IgG does not readily cross the blood-brain barrier, and lesions of peripheral terminals should not cause cell death. This study was designed to explore the distribution of central neural damage and to investigate features that might account for vulnerability. Rat spinal cord and brainstem were stained for choline acetyltransferase (ChAT) and nitric oxide synthase (NOS) immunoreactivity. Four months after administration of AChE antibodies, ChAT-positive neurons in the intermediolateral nucleus (IML) were 61-66% fewer throughout the thoracolumbar cord (T1, T2, T8, T12, L1). NOS-positive neurons in these loci were affected to the same extent by antibody-treatment, although they were only two-thirds as numerous. By contrast, neurons in the central autonomic nucleus of the thoracolumbar cord were scarcely affected. These results point to immunochemical differences in the central autonomic outflow, which may partially explain the puzzling selectivity of neural damage in AChE immunolesioning. Different results were obtained after guanethidine sympathectomy, which ablated nearly all neurons in the superior cervical ganglion without any effect on preganglionic neurons in the IML. Therefore, if the central effects of antibodies are indirectly mediated by loss of trophic support from the periphery, this support cannot arise from adrenergic neurons but must come from other ganglionic cells.
Department of Pharmacology, Mayo Clinic, Mayo Foundation, 200 First Street S.W., Rochester, Minnesota, 55905, USA.
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H
Tang
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Hammond
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Brimijoin
D000110:Acetylcholinesterase / Q000032:analysis*; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000201:enzymology*; D001933:Brain Stem / Q000166:cytology*; D002452:Cell Count; D048429:Cell Size; D007150:Immunohistochemistry; D008161:Lumbosacral Region; D008297:Male; D019001:Nitric Oxide Synthase / Q000032:analysis; D010275:Parasympathetic Nervous System / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology*; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000166:cytology / Q000201:enzymology*
D019001:Nitric Oxide Synthase; D000110:Acetylcholinesterase