Abstract
A nerve growth factor (NGF)-diphtheria toxin conjugate (NGDT) was found to selectively abolish or depress the activity of NGF receptor-bearing cholinergic neurons of the basal magnocellular nucleus (BMN). Bilateral cortical injections of NGDT impaired the retention of passive avoidance behavior in mice. A memory deficit was also revealed when cortical injections of NGDT were administered after the acquisition of a passive avoidance response. Thus, retrograde destruction of BMN cholinergic neurons by the cortical injection of NGDT interfered with both learning and memory processes. The animal model outlined here should be useful in analyzing the pathogenesis of Alzheimer's disease and the functions of the cholinergic system in the BMN.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Avoidance Learning / drug effects
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Avoidance Learning / physiology*
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Behavior, Animal / physiology*
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Brain / cytology
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Brain / drug effects
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Brain / metabolism
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Cerebral Cortex / drug effects
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Choline O-Acetyltransferase / metabolism
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Diphtheria Toxin / pharmacology
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Histocytochemistry
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Immunohistochemistry
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Injections
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Male
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Medulla Oblongata / cytology
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Medulla Oblongata / physiology*
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Mice
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Nerve Growth Factors / metabolism
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Nerve Growth Factors / pharmacology
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Neurons / metabolism
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Parasympathetic Nervous System / physiology*
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Rats
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Rats, Inbred Strains
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Receptors, Cell Surface / metabolism
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Receptors, Nerve Growth Factor
Substances
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Diphtheria Toxin
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Nerve Growth Factors
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Receptors, Cell Surface
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Receptors, Nerve Growth Factor
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Choline O-Acetyltransferase