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Spatial learning impairments in rats with selective immunolesion of the forebrain cholinergic system

Nilsson, O G LU ; Leanza, G LU ; Rosenblad, C LU ; Lappi, D A ; Wiley, R G and Björklund, A LU orcid (1992) In NeuroReport 3(11). p.8-1005
Abstract

A monoclonal antibody to the low-affinity NGF receptor, 192 IgG, coupled to a cytotoxin, saporin, was recently introduced as an efficient selective neurotoxin for the NGFr-bearing cholinergic neurones in the rat basal forebrain. In the present study we report that an intracerebroventricular injection of this 192 IgG-saporin conjugate induces a severe, long-lasting spatial learning impairment, as assessed in the Morris water-maze task. This behavioural impairment was associated with 65-90% depletion of choline acetyltransferase activity (ChAT) in the hippocampus and cortex. ChAT activity associated with other cholinergic neurone systems in the brain (striatum, mesencephalon, spinal cord), was left virtually unaffected. This new... (More)

A monoclonal antibody to the low-affinity NGF receptor, 192 IgG, coupled to a cytotoxin, saporin, was recently introduced as an efficient selective neurotoxin for the NGFr-bearing cholinergic neurones in the rat basal forebrain. In the present study we report that an intracerebroventricular injection of this 192 IgG-saporin conjugate induces a severe, long-lasting spatial learning impairment, as assessed in the Morris water-maze task. This behavioural impairment was associated with 65-90% depletion of choline acetyltransferase activity (ChAT) in the hippocampus and cortex. ChAT activity associated with other cholinergic neurone systems in the brain (striatum, mesencephalon, spinal cord), was left virtually unaffected. This new immunotoxin holds great promise as a tool for selective and efficient lesions of the forebrain cholinergic system in functional and behavioural studies.

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@article{2c87af5f-69f3-468e-8696-fa4f5d276ed8,
  abstract     = {{<p>A monoclonal antibody to the low-affinity NGF receptor, 192 IgG, coupled to a cytotoxin, saporin, was recently introduced as an efficient selective neurotoxin for the NGFr-bearing cholinergic neurones in the rat basal forebrain. In the present study we report that an intracerebroventricular injection of this 192 IgG-saporin conjugate induces a severe, long-lasting spatial learning impairment, as assessed in the Morris water-maze task. This behavioural impairment was associated with 65-90% depletion of choline acetyltransferase activity (ChAT) in the hippocampus and cortex. ChAT activity associated with other cholinergic neurone systems in the brain (striatum, mesencephalon, spinal cord), was left virtually unaffected. This new immunotoxin holds great promise as a tool for selective and efficient lesions of the forebrain cholinergic system in functional and behavioural studies.</p>}},
  author       = {{Nilsson, O G and Leanza, G and Rosenblad, C and Lappi, D A and Wiley, R G and Björklund, A}},
  issn         = {{0959-4965}},
  keywords     = {{Acetylcholinesterase/immunology; Animals; Antibodies, Monoclonal; Antineoplastic Agents, Phytogenic/toxicity; Brain Chemistry; Choline O-Acetyltransferase/metabolism; Female; Histocytochemistry; Immunotoxins/administration & dosage; Injections, Intraventricular; Learning/physiology; N-Glycosyl Hydrolases; Parasympathetic Nervous System/physiology; Plant Proteins/toxicity; Prosencephalon/physiology; Rats; Rats, Sprague-Dawley; Receptors, Nerve Growth Factor/immunology; Ribosome Inactivating Proteins, Type 1; Saporins; Space Perception/physiology}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{8--1005}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{NeuroReport}},
  title        = {{Spatial learning impairments in rats with selective immunolesion of the forebrain cholinergic system}},
  url          = {{https://journals.lww.com/neuroreport/pages/articleviewer.aspx?year=1992&issue=11000&article=00015&type=abstract}},
  volume       = {{3}},
  year         = {{1992}},
}