Leanza G, Nilsson O, Wiley RG, Bjorklund A (1993) Dose-related effects of 192 IgG-saporin on basal forebrain cholinergic neurons: Biochemical, immunocytochemical and behavioral studies on neonatal and adult rats. Neuroscience 1993 Abstracts 771.12.
Summary: Highly selective and efficient depletions of the NGF receptor-positive cholinergic neurons in the basal forebrain, associated with profound behavioral changes, have been reported after treatment with 192 IgG-saporin, a recently introduced immunotoxin. In the present study, the effects of different doses of the toxin conjugate were compared following bilateral injections in the lateral ventricles of infant (2-3 days post-natal, 0.2 to 0.8 µg dose-range) and adult rats (1.25 to 10 µg dose-range). Five to eight weeks post-injection, dose-related behavioral effects of the lesion were evaluated in water maze, passive avoidance and locomotor activity tests, followed by biochemical and histologic analyses performed on tissue specimens. In the adult rats, the immunotoxin produced severe dose-dependent cognitive deficits in water maze task performance and passive avoidance retention that correlated with decline in choline acetyltransferase (ChAT) activity in neocortical and hippocampal areas (up to 95% reduction) and depletion of NGF receptor-positive neurons in the septal-diagonal band area and nucleus basalis (>95%). Similar dose-related patterns of ChAT activity reduction and neuronal loss throughout the basal forebrain were seen in rats neonatałly injected with the immunotoxin. ChAT levels in other regions such as brainstem, cerebellum or the spinal cord were found largely unaffected in both adult and neonatałly lesioned rats. The present results confirm 192 IgG-saporin as a powerful tool to induce specific and robust cholinergic lesions either during development or adulthood and emphasize the crucial role of the forebrain cholinergic system in cognitive functions.
Related Products: 192-IgG-SAP (Cat. #IT-01)