Elsevier

Neuroscience Letters

Volume 452, Issue 3, 20 March 2009, Pages 247-251
Neuroscience Letters

Efficacy of a murine-p75-saporin immunotoxin for selective lesions of basal forebrain cholinergic neurons in mice

https://doi.org/10.1016/j.neulet.2009.01.006Get rights and content

Abstract

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 μL of either saline or murine-p75NTR-saporin (0.65 μg/μL or 1.3 μg/μL) 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.

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Acknowledgements

The immunotoxin was provided generously by Dr. Douglas Lappi, Advanced Targeting Systems. We would like to express our thanks to Ms. Patience Carey and Ms. Ginny Quinan for their excellent care of our animals. This project was supported by NIH 5R44-NS034591.

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