Efficacy of a murine-p75-saporin immunotoxin for selective lesions of basal forebrain cholinergic neurons in mice.
Selective lesioning of cholinergic neurons in the basal forebrain provides a tool for examining the functional significance of cholinergic loss, which is associated with a number of developmental and neurodegenerative disorders. A new version of an immunotoxin (murine-p75NTR-saporin) was used to produce a selective loss of cholinergic neurons in the adult basal forebrain of the mouse. This new version of the toxin is significantly more potent and selective than a previously developed version. C57Bl/6J mice (n=30) were given 1 microL of either saline or murine-p75NTR-saporin (0.65 microg/microL or 1.3 microg/microL) into the lateral ventricles, and then sacrificed 10-12 days post-surgery for histological analysis. In contrast to results from the previous version of the toxin, survival of the toxin-treated mice was 100% at both doses. A complete loss of cholinergic neurons was seen in the medial septum (MS) with both doses, while a dose-dependent loss of cholinergic neurons was observed in the nucleus basalis magnocellularis (nBM). The lesions were associated with locomotor hypoactivity and anxiolytic-type behavioral effects. These studies describe the efficacy and selectivity of this new version of murine-p75NTR-saporin, which may be used to provide insight into functional deficits that result from the loss of cholinergic neurons in the mouse basal forebrain.
Nag
Nupur
N
Department of Biological Sciences, Wellesley College, Wellesley, MA 02481, USA.
Baxter
Mark G
MG
Berger-Sweeney
Joanne E
JE
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001007:Anxiety; D020532:Basal Nucleus of Meynert / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005455:Fluorescent Antibody Technique; D000922:Immunotoxins / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009026:Mortality; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry*; D054789:Ribosome Inactivating Proteins, Type 1 / Q000737:chemistry* / Q000633:toxicity*; D000076985:Saporins; D020665:Septum of Brain / Q000187:drug effects
D000922:Immunotoxins; D017475:Receptors, Nerve Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; C517634:Ngfr protein, mouse; D000076985:Saporins; D000109:Acetylcholine