Stereotactic lesioning of cholinergic cells by injection of ME20.4 Saporin in the nucleus basalis of Meynert in a rhesus monkey (Macaca mulatta).

Abstract

Cholinergic degeneration in the nucleus basalis of Meynert (NBM) is clinically linked to cognitive impairment and gait dysfunction in Alzheimer's disease and Parkinson's disease. Modeling cholinergic degeneration in an animal model may provide powerful opportunities to study the clinical-physiological role of the NBM and lead to new therapies. We describe a procedure to inject ME20.4 Saporin, an immunotoxin that specifically binds to and depletes cholinergic neurons stereotactically into the NBM of a rhesus monkey (Macaca mulatta). A digital non-human primate brain atlas was co-registered to the brain of the monkey. A custom-designed cranial chamber was also implanted to the skull to guide the injection. The effects of the ME20.4 Saporin injections were evaluated in vivo with PET-CT using [18F]-FEOBV as a radiotracer. This approach yielded reliable spatial accuracy and successful delivery of ME20.4 Saporin into the NBM. [18F]-FEOBV PET analyses revealed reduced radiotracer uptake in the NBM. Postmortem assessment showed a reduction of ME20.4-positive cells within the NBM. No clear effects on cognitive testing were observed. This Saporin-mediated selective destruction of cholinergic neurons in the NBM, using MRI-guidance and a cranial chamber, offers a promising method to study the pathophysiology of NBM degeneration and possible therapeutic interventions.