title: Differential changes in rat cholinergic parameters subsequent to immunotoxic lesion of the basal forebrain nuclei.
abstract: The degree of lesion produced by 192 IgG-saporin relative to controls was compared using three independent methods. Microdialyzed acetylcholine (ACh), choline acetyltransferase (ChAT) activity, and the rate of ACh synthesis were compared in the frontal cortex and hippocampus. Microdialysis of rats was performed 1 and 15 weeks post-lesion. In week 16, the rats were sacrificed after an injection of deuterated choline (Ch) for determination of the rate of ACh synthesis. ChAT activity was determined at the same timepoints in a separate set of rats. At 1 week, ChAT activity and microdialyzed ACh showed similar degrees of depletion. At 15 weeks, microdialyzed ACh was significantly lower than the synthesis rate in cortex, but not in hippocampus. A small increase in ChAT activity between 1 and 15 weeks was found in the cortex, but not hippocampus. In the hippocampus, however, the rate of ACh synthesis was significantly greater than ChAT activity. This was true for two doses of immunotoxin; the greater compensation occurring with the lesser lesion. Microdialyzed ACh levels were not different from the other measures in hippocampus. Residual cholinergic terminals in the hippocampus, but not frontal cortex, compensate for a selective cholinergic lesion by increasing the rate of synthesis and may thereby alleviate hippocampus-dependent behavioral deficits.
authors.affiliation: Department of Neurosciences, 9151, University of California at San Diego, La Jolla, CA 92093, USA. jwaite@ucsd.edu
authors.forename: J J
authors.initials: JJ
authors.lastname: Waite
authors.forename: A D
authors.initials: AD
authors.lastname: Chen
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D020532:Basal Nucleus of Meynert / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D000922:Immunotoxins / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009699:N-Glycosyl Hydrolases; D009434:Neural Pathways / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012686:Septal Nuclei / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
chemical_list: 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; D000109:Acetylcholine