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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-5-27
pubmed:abstractText
The selective lesion of basal forebrain cholinergic neurons (BFCNs) is an unestimable tool to study the implication of these neurons in cognition, an interest widely motivated by their degeneration in Alzheimer's disease. Here we evaluated the histochemical and behavioral effects of a selective lesion of BFCNs in C57BL/6J mice treated intracerebroventricularly (ICV) with a novel version of the immunotoxin mu p75-saporin (0.4 mug/mouse). There was a 100% postsurgical survival rate, no abnormal loss of weight, no disruption of sensorimotor coordination, and no noncognitive bias in a water-maze test. This immunotoxin induced a loss of choline acetyltransferase-positive neurons in the medial septum (-82%) and in the nucleus basalis (-55%). Preserved parvalbumine-immunostaining suggests that the lesion was specific to BFCNs. Septo-hippocampal and basalo-cortical projections of BFCNs degenerated as suggested by massive loss of acetylcholinesterase-positive staining in the hippocampus and the cortical mantle. Moreover, anticalbindin immunostaining showed no damage to cerebellar Purkinje cells. Lesioned mice displayed increased diurnal and nocturnal locomotor activity. Their spatial learning/memory performances in a water maze and in a Barnes maze were significantly impaired: learning was substantially slowed down, although not obliterated, and memory retention was altered. These behavioral consequences are comparable, with fewer side effects, to those reported after ICV 192 IgG-saporin in rats. In conclusion, the new version of mu p75-saporin provides a safe and powerful tool for BFCN lesion in mice.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1098-1063
pubmed:author
pubmed:copyrightInfo
(c) 2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
610-22
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18306300-Acetylcholinesterase, pubmed-meshheading:18306300-Alzheimer Disease, pubmed-meshheading:18306300-Animals, pubmed-meshheading:18306300-Calcium-Binding Protein, Vitamin D-Dependent, pubmed-meshheading:18306300-Choline O-Acetyltransferase, pubmed-meshheading:18306300-Cholinergic Antagonists, pubmed-meshheading:18306300-Cognition Disorders, pubmed-meshheading:18306300-Disease Models, Animal, pubmed-meshheading:18306300-Immunotoxins, pubmed-meshheading:18306300-Injections, Intraventricular, pubmed-meshheading:18306300-Locomotion, pubmed-meshheading:18306300-Male, pubmed-meshheading:18306300-Maze Learning, pubmed-meshheading:18306300-Memory Disorders, pubmed-meshheading:18306300-Mice, pubmed-meshheading:18306300-Mice, Inbred C57BL, pubmed-meshheading:18306300-Motor Activity, pubmed-meshheading:18306300-Nerve Tissue Proteins, pubmed-meshheading:18306300-Neurons, pubmed-meshheading:18306300-Parvalbumins, pubmed-meshheading:18306300-Postural Balance, pubmed-meshheading:18306300-Prosencephalon, pubmed-meshheading:18306300-Retention (Psychology)
pubmed:year
2008
pubmed:articleTitle
Neuroanatomical and behavioral effects of a novel version of the cholinergic immunotoxin mu p75-saporin in mice.
pubmed:affiliation
Laboratoire d'Imagerie et de Neurosciences Cognitives, UMR7191 CNRS, Equipe de Neurobiologie Cognitive et Comportementale, ULP, IFR 37 de Neurosciences, GDR 2905 CNRS, 12 rue Goethe, 67000 STRASBOURG, France. chantal.mathis@linc.u-strasbg.fr
pubmed:publicationType
Journal Article