TY - JOUR
T1 - Efficacy of a murine-p75-saporin immunotoxin for selective lesions of basal forebrain cholinergic neurons in mice
AU - Nag, Nupur
AU - Baxter, Mark
AU - Berger-Sweeney, Joanne
PY - 2009
Y1 - 2009
N2 - 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 ?L of either saline or murine-p75NTR-saporin (0.65 ?g/?L or 1.3 ?g/?L) 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.
AB - 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 ?L of either saline or murine-p75NTR-saporin (0.65 ?g/?L or 1.3 ?g/?L) 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.
UR - http://www.sciencedirect.com.ezproxy.lib.monash.edu.au/science/article/pii/S0304394009000147
U2 - 10.1016/j.neulet.2009.01.006
DO - 10.1016/j.neulet.2009.01.006
M3 - Article
VL - 452
SP - 247
EP - 251
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 3
ER -