Abstract
A monoclonal antibody to the rat nerve growth factor (NGF) receptor, 192 IgG, accumulates bilaterally and specifically in cholinergic basal forebrain (CBF) cells following intraventricular injection. An immunotoxin composed of 192 IgG linked to saporin (192 IgG-saporin) has been shown to destroy cholinergic neurons in the basal forebrain. We sought to determine if intraventricular 192 IgG-saporin affected choline acetyltransferase (ChAT) enzyme activity in the CBF terminal projection fields. ChAT assays from 192 IgG-saporin-treated animals showed significant time-dependent decreases in ChAT activity in the neocortex, olfactory bulb and hippocampus, compared to PBS- or OKT1-saporin-injected controls. ChAT and tyrosine hydroxylase activity in the striatum was always unchanged by 192 IgG-saporin. ChAT immunohistochemistry was confirmative of major cell loss in the CBF, while other cholinergic nuclei appeared unremarkable. The data provide further evidence of the selectivity of 192 IgG-saporin in abolishing cholinergic, NGF receptor-positive CNS neurons.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylcholine / physiology*
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Animals
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Antibodies, Monoclonal
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Cerebral Cortex / drug effects
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Cerebral Cortex / enzymology
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Choline O-Acetyltransferase / drug effects*
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Female
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Hippocampus / drug effects
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Hippocampus / enzymology
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Immunoenzyme Techniques
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Immunoglobulin G / toxicity*
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Immunotoxins
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Injections, Intraventricular
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N-Glycosyl Hydrolases
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Neurons / chemistry
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Neurons / drug effects*
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Olfactory Bulb / drug effects
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Olfactory Bulb / enzymology
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Plant Proteins / toxicity*
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Prosencephalon / chemistry
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Prosencephalon / cytology
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Prosencephalon / drug effects*
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Rats
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Rats, Sprague-Dawley
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Receptors, Nerve Growth Factor / analysis*
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Ribosome Inactivating Proteins, Type 1
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Saporins
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Tyrosine 3-Monooxygenase / drug effects
Substances
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192 IgG-saporin
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Antibodies, Monoclonal
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Immunoglobulin G
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Immunotoxins
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Plant Proteins
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Receptors, Nerve Growth Factor
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Ribosome Inactivating Proteins, Type 1
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Tyrosine 3-Monooxygenase
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Choline O-Acetyltransferase
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N-Glycosyl Hydrolases
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Saporins
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Acetylcholine