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Selective lesioning of the basal forebrain cholinergic system by intraventricular 192 IgG-saporin : behavioural, biochemical and stereological studies in the rat

Leanza, G LU ; Nilsson, O G LU ; Wiley, R G and Björklund, A LU (1995) In European Journal of Neuroscience 7(2). p.329-343
Abstract

The elucidation of the functional role of the basal forebrain cholinergic system will require access to a highly specific and efficient cholinergic neurotoxin. Recently, selective depletion of the nerve growth factor (NGF) receptor-bearing cholinergic neurons in the rat basal forebrain and a dramatic loss of cholinergic innervation in the related cortical regions have been obtained following intraventricular injection of a newly introduced immunotoxin, 192 IgG-saporin. Here we extend these initial findings and report that administration of increasing doses (1.25, 2.5, 5.0 or 10 micrograms) of the 192 IgG-saporin conjugate into the lateral ventricles of adult rats induced dose-dependent impairments in the water maze task and passive... (More)

The elucidation of the functional role of the basal forebrain cholinergic system will require access to a highly specific and efficient cholinergic neurotoxin. Recently, selective depletion of the nerve growth factor (NGF) receptor-bearing cholinergic neurons in the rat basal forebrain and a dramatic loss of cholinergic innervation in the related cortical regions have been obtained following intraventricular injection of a newly introduced immunotoxin, 192 IgG-saporin. Here we extend these initial findings and report that administration of increasing doses (1.25, 2.5, 5.0 or 10 micrograms) of the 192 IgG-saporin conjugate into the lateral ventricles of adult rats induced dose-dependent impairments in the water maze task and passive avoidance retention, but only weak and inconsistent effects on locomotor activity. These behavioural changes were paralleled by a reduction in choline acetyltransferase activity in hippocampus and several cortical areas (up to 97%) and selective depletions of NGF receptor-positive cholinergic neurons in the septal-diagonal band area and nucleus basalis magnocellularis (up to 99%). By contrast, the non-cholinergic parvalbumin-containing neurons in the septum were completely spared, and other cholinergic projection systems (such as in the striatum, thalamus, brainstem and spinal cord) were unaffected even at the highest dose. The observed changes in the water maze and passive avoidance tasks, as well as the cholinergic cell loss, were maintained up to at least 8 months following the intraventricular injection of a single dose (5 micrograms) of the immunotoxin. The results confirm the usefulness of the 192 IgG-saporin toxin for selective and profound lesions of the basal forebrain cholinergic neurons and provide further support for a role of the basal forebrain cholinergic system in cognitive functions.

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keywords
Acetylcholinesterase/analysis, Animals, Antibodies, Monoclonal/administration & dosage, Avoidance Learning/drug effects, Cholinergic Agents/administration & dosage, Female, Histocytochemistry, Immunotoxins/administration & dosage, Injections, Intraventricular, Maze Learning/drug effects, Motor Activity/drug effects, N-Glycosyl Hydrolases, Neurons/chemistry, Parvalbumins/analysis, Prosencephalon/physiology, Rats, Rats, Sprague-Dawley, Ribosome Inactivating Proteins, Type 1, Saporins
in
European Journal of Neuroscience
volume
7
issue
2
pages
329 - 343
publisher
Wiley-Blackwell
external identifiers
  • pmid:7757267
  • scopus:0028815497
ISSN
0953-816X
DOI
10.1111/j.1460-9568.1995.tb01068.x
language
English
LU publication?
yes
id
dd781d89-269d-4569-9866-b2ce86447551
date added to LUP
2019-06-25 09:53:51
date last changed
2020-01-13 02:06:16
@article{dd781d89-269d-4569-9866-b2ce86447551,
  abstract     = {<p>The elucidation of the functional role of the basal forebrain cholinergic system will require access to a highly specific and efficient cholinergic neurotoxin. Recently, selective depletion of the nerve growth factor (NGF) receptor-bearing cholinergic neurons in the rat basal forebrain and a dramatic loss of cholinergic innervation in the related cortical regions have been obtained following intraventricular injection of a newly introduced immunotoxin, 192 IgG-saporin. Here we extend these initial findings and report that administration of increasing doses (1.25, 2.5, 5.0 or 10 micrograms) of the 192 IgG-saporin conjugate into the lateral ventricles of adult rats induced dose-dependent impairments in the water maze task and passive avoidance retention, but only weak and inconsistent effects on locomotor activity. These behavioural changes were paralleled by a reduction in choline acetyltransferase activity in hippocampus and several cortical areas (up to 97%) and selective depletions of NGF receptor-positive cholinergic neurons in the septal-diagonal band area and nucleus basalis magnocellularis (up to 99%). By contrast, the non-cholinergic parvalbumin-containing neurons in the septum were completely spared, and other cholinergic projection systems (such as in the striatum, thalamus, brainstem and spinal cord) were unaffected even at the highest dose. The observed changes in the water maze and passive avoidance tasks, as well as the cholinergic cell loss, were maintained up to at least 8 months following the intraventricular injection of a single dose (5 micrograms) of the immunotoxin. The results confirm the usefulness of the 192 IgG-saporin toxin for selective and profound lesions of the basal forebrain cholinergic neurons and provide further support for a role of the basal forebrain cholinergic system in cognitive functions.</p>},
  author       = {Leanza, G and Nilsson, O G and Wiley, R G and Björklund, A},
  issn         = {0953-816X},
  language     = {eng},
  number       = {2},
  pages        = {329--343},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Neuroscience},
  title        = {Selective lesioning of the basal forebrain cholinergic system by intraventricular 192 IgG-saporin : behavioural, biochemical and stereological studies in the rat},
  url          = {http://dx.doi.org/10.1111/j.1460-9568.1995.tb01068.x},
  doi          = {10.1111/j.1460-9568.1995.tb01068.x},
  volume       = {7},
  year         = {1995},
}