Intraparenchymal infusions of 192 IgG-saporin: development of a method for selective and discrete lesioning of cholinergic basal forebrain nuclei.
The immunotoxin 192 IgG-saporin has a high degree of selectivity for cholinergic neurons within the basal forebrain (CBF). Intracerebroventricular delivery of 192 IgG-saporin results in a diffuse and massive depletion of choline acetyltransferase (ChAT) activity in projections of the CBF, and non-selective loss of Purkinje cells. To dissociate the basal-cortical and septo-hippocampal cholinergic systems and to minimize non-specific effects, we developed intraparenchymal parameters to deliver 192 IgG-saporin discretely to either the nucleus basalis magnocellularis (NBM) or the medial septum (MS). Intraparenchymal administration of the immunotoxin into the NBM or MS resulted in a dose-dependent depletion of ChAT activity in the corresponding projection areas and a concomitant loss of ChAT immunoreactive neurons in both nuclei. Both lesions were regionally restricted, having a minimal diffusion into adjacent CBF nuclei. Control infusions did not result in non-specific parenchymal damage. In addition, immunotoxic infusions had no effect on monoamine neurotransmitter systems. By optimizing the dosages for both CBF nuclei, we maximized ChAT depletion while minimizing diffusion into the adjacent CBF nuclei. This study delineated injection parameters enabling a selective dissociation of two cholinergic subpopulations in the basal forebrain for further functional characterization.
Pizzo
D P
DP
Department of Neurosciences, University of California San Diego, La Jolla 92093-0624, USA.
Waite
J J
JJ
Thal
L J
LJ
Winkler
J
J
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000633:toxicity; D020532:Basal Nucleus of Meynert / Q000166:cytology*; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000008:administration & dosage* / Q000633:toxicity; D002799:Cholinergic Fibers; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000008:administration & dosage* / Q000633:toxicity; D007276:Injections, Intraventricular; D008297:Male; D009699:N-Glycosyl Hydrolases; D016548:Prosencephalon / Q000166:cytology; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D020665:Septum of Brain / Q000166:cytology / Q000201:enzymology
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D002795:Choline O-Acetyltransferase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins