title: Alterations of choline acetyltransferase, phosphoinositide hydrolysis, and cytoskeletal proteins in rat brain in response to colchicine administration.
abstract: Colchicine, a microtubule disrupting toxin, was administered intracerebroventricularly to rats, followed by measurements of (i) the activity of choline acetyltransferase, a biochemical marker of cholinergic neurons, (ii) cytoskeletal protein concentrations, including tau, MAP-2, spectrin, and tubulin, and (iii) the activity of the second messenger-generating system, receptor-coupled phosphoinositide hydrolysis. One week after colchicine treatment there was a 60% decrease in choline acetyltransferase activity in the hippocampus, which was followed by a gradual increase in only a 29% deficit after 12 weeks. In the striatum and cerebral cortex, choline acetyltransferase activity was slightly reduced (by 13% and 19%, respectively) 1 week after colchicine treatment followed by increases to control values. The concentrations of tau and tubulin in the hippocampus were unaltered by colchicine treatment, and MAP-2 and spectrin were only slightly reduced 4 weeks after colchicine. Hippocampal phosphoinositide hydrolysis induced by norepinephrine was elevated approximately 28% 1 and 2 weeks after colchicine treatment and that induced by ibotenate was increased by 53% 2 weeks after colchicine. These results demonstrate that colchicine causes a severe depletion of choline acetyltransferase 1 week after administration. There was not a significant reduction of the concentration of any of the cytoskeletal proteins after 1 week, possibly due to the cell-selectivity of the toxic effect of colchicine, but there was a delayed, and temporary, decline of MAP-2 and spectrin concentrations. Associated with the decreased choline acetyltransferase activity after 1 week was an enhanced phosphoinositide hydrolysis in response to norepinephrine, and after 2 weeks there were enhanced responses to norepinephrine and to ibotenate.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama, Birmingham 35294.
authors.forename: K
authors.initials: K
authors.lastname: Kolasa
authors.forename: R S
authors.initials: RS
authors.lastname: Jope
authors.forename: M S
authors.initials: MS
authors.lastname: Baird
authors.forename: G V
authors.initials: GV
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003078:Colchicine / Q000008:administration & dosage / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D007294:Inositol / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009928:Organ Specificity; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D003598:Cytoskeletal Proteins; D010716:Phosphatidylinositols; D007294:Inositol; D002795:Choline O-Acetyltransferase; D003078:Colchicine