Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of bilateral colchicine lesions of the nucleus basalis magnocellularis (NBM) on agonist-stimulated phosphoinositide (PI) hydrolysis was examined in cortical slices 1, 3, or 14 months after surgery. Colchicine lesions resulted in a loss of acetylcholinesterase staining in the cortex which recovered to control levels by 14 months. Choline acetyltransferase activity in the cortex was decreased by 43% one month after lesioning, but returned to control levels by 3 months. In vitro stimulation with carbachol produced a concentration-dependent increase in PI hydrolysis, which was enhanced 3 and 14 months after NBM lesions. Norepinephrine and quisqualate-stimulated PI hydrolysis was also enhanced 14 months after NBM lesions. These results suggest a slow up-regulation of postsynaptic receptor function following presynaptic loss of transmitter.
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PMID:Long-term changes in phosphoinositide hydrolysis following colchicine lesions of the nucleus basalis magnocellularis. 165 Nov 50

It has been proposed that hippocampal rhythmical slow wave activity (RSA or theta-rhythm) induced by sensory stimulation (atropine-sensitive theta) is generated by the cholinergic septo-hippocampal system. Although ablations of the septum or its projections to the hippocampus disrupt hippocampal RSA, such non-selective lesions damage both cholinergic and non-cholinergic septo-hippocampal inputs. The present study assesses the effects of a selective septal neurotoxic lesion on hippocampal electrical activity. Colchicine, which has been reported to be selectively toxic to cholinergic neurons in the medial septum, was injected into the right lateral ventricle, and electrodes were implanted bilaterally into the dorsal hippocampus of female Sprague-Dawley rats. Hippocampal electrical activity was recorded 10-14 days later from the ipsilateral (colchicine-treated) and contralateral (control) hemispheres during locomotor activity or immobility. RSA ranging from 6.3 to 8.7 Hz was evoked in both hippocampi during mobility. Following i.p. administration of an anesthetic dose of urethane, hippocampal RSA at a frequency of 4 Hz could be elicited in the control hemisphere (n = 12) of all animals by pinching the tail. RSA was absent in 6 of 9 animals in the colchicine-treated hemisphere. RSA from control and treated hemispheres persisting after urethane administration was abolished by 5 mg/kg of scopolamine, thus verifying its cholinergic nature. A decrease in the number of choline acetyltransferase (ChAT)-immunoreactive neurons in the medial septum and a depletion of acetylcholinesterase (AChE)-staining in the hippocampus were evident in the hemisphere ipsilateral to colchicine administration. These data support the septal pacemaker hypothesis of hippocampal theta-rhythm and further demonstrate the neurotoxic effect of colchicine on septo-hippocampal cholinergic neurons by the induction of a functional alteration. The selective disruption of cholinergic neurons in the medial septum by colchicine provides a means to dissociate the contribution of septal cholinergic and non-cholinergic components to hippocampal electrical activity.
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PMID:Colchicine-induced deafferentation of the hippocampus selectively disrupts cholinergic rhythmical slow wave activity. 172 36

Ganglioside AGF2 prevented the cognitive and locomotor alterations induced by intraventricular colchicine. Adult male rats were initially trained to perform a standard radial arm maze (RAM) task. Following training, they were injected intraperitoneally with 10 mg/kg AGF2 (COL/AGF2), cerebrospinal fluid (CSF/AGF2) or the saline vehicle (COL/SAL, CSF/SAL) for 3 days prior to and for 14 days following the bilateral injection of colchicine (7 micrograms/0.5 microliters) or artificial CSF into the lateral ventricles. Colchicine (COL/SAL) impaired performance of the standard RAM task as well as a working memory version of the task in which various delays were imposed between the fourth and fifth arm choices. Colchicine also produced a transient hyperactivity which subsided within 10 weeks following surgery. In contrast, AGF2 (COL/AGF2) prevented the impairments in RAM performance and the alterations in locomotor behavior. Colchicine also produced significant decreases in hippocampal ChAT activity and high affinity choline uptake that were prevented by prior treatment with AGF2. Finally, colchicine produced a 35% decrease in the number of acetylcholinesterase-positive (cholinergic) neurons in the medial septum and vertical limb of the diagonal band (MS/VLDB) which was also prevented by AGF2. Thus, the behavioral and neurochemical protection afforded by AGF2 was paralleled by a prevention of the loss of hippocampal cholinergic parameters and cholinergic neurons in the MS/VLDB.
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PMID:Ganglioside AGF2 prevents the cognitive impairments and cholinergic cell loss following intraventricular colchicine. 202 33

Bilateral injections of colchicine (3.5 or 7.0 micrograms/0.5 microliters/site) into either the dentate gyrus or the lateral cerebroventricles (i.c.v.) of Sprague-Dawley rats produced specific behavioral, histopathological and neurochemical alterations. Colchicine, administered via either route, produced impairments in the performance of a radial-arm maze task which did not subside during 8 weeks of testing. Intradentate colchicine decreased (1) the thickness of both blades of the dentate granule cell layer, (2) the size of the overlying molecular layer, (3) hippocampal volume, and (4) the number of cholinergic neurons in the medial septum/vertical limb of the diagonal band (MS/VLDB). I.c.v. administration of colchicine did not alter any index of hippocampal morphology but did significantly decrease the number of cholinergic neurons in the MS/VLDB. An analysis of the time course of cholinotoxicity revealed that both intradentate and i.c.v. colchicine decreased choline acetyltransferase (ChAT) activity and high affinity choline uptake (HAChU) in the hippocampus at 1 and 3, but not 9, weeks following surgery. Furthermore, i.c.v. colchicine decreased ChAT activity in the septum at both 3 and 9 weeks following surgery. Neither route of administration altered ChAT or HAChU in the frontal cortex, olfactory bulb or striatum. The decreases in presynaptic cholinergic parameters were paralleled by a reduction in acetylcholinesterase staining in the hippocampus which appeared to recover within 9 weeks. These data suggest that intradentate colchicine produces either (i) transsynaptic degeneration of cholinergic neurons due to a loss of their target sites (granule cells in the dentate gyrus), (ii) a direct cholinotoxic effect, or (iii) a combination of these mechanisms. The i.c.v. injection of colchicine appears to exert a direct toxic effect on cholinergic neurons and/or nerve terminals that results in the death of these neurons. Colchicine may be a useful tool for investigating the behavioral and neurobiological properties of the septohippocampal cholinergic pathway and its response to injury.
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PMID:Cholinergic cell loss and cognitive impairments following intraventricular or intradentate injection of colchicine. 237 86

Lesions in the nucleus basalis in the rat are known to decrease presynaptic markers for acetylcholine, including levels of cholineacetyltransferase (CHAT), high affinity uptake of choline and levels of acetylcholinesterase. Effects of lesions of the nucleus basalis on populations of nicotinic and muscarinic receptors are less well understood. After bilateral injection of the neurotoxic agent, colchicine into the nucleus basalis in the rat, levels of CHAT in the cerebral cortex were reduced 44%. Muscarinic cholinergic [( 3H]QNB) and dopaminergic [( 3H]spiroperidol) binding was not changed in the cortex, hippocampus or striatum. However, significant decreases in nicotinic binding sites, labelled by [( 3H]acetylcholine), were observed in the frontal cortex of nucleus basalis treated animals; scatchard plot analysis indicated a significant decrease in the number, but not affinity, of nicotinic binding sites. Colchicine injected into the nucleus basalis had no effect on the binding of [3H]acetylcholine in the hippocampus, but decreased binding of [3H]acetylcholine in the striatum. Subsequent experiments, in which colchicine was administered into the striatum at a site above the nucleus basalis had no significant effect on nicotinic binding in the striatum or frontal cortex. These results support the hypothesis that degeneration of the nucleus-basalis-cortical cholinergic pathway results in a loss of presynaptic nicotinic binding sites in the cortex as well as in the striatum (through transsynaptic degeneration of the cortico-striatal pathway).
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PMID:Colchicine administered into the area of the nucleus basalis decreases cortical nicotinic cholinergic receptors labelled by [3H]-acetylcholine. 277 54

Colchicine, injected bilaterally into the forebrain of day-old chicks at times before and after one-trial avoidance learning, produced transient amnesia for one to three hours after learning, that could not be accounted for as a perceptual or attentional defect. The amnesia was dose dependent and was produced only when injections occurred within a limited period before and after learning. No amnesia occurred when injections were given 120 min before or 60 min later than the learning trial, nor at times prior to the retrieval test. During the amnesic period, new learning could occur and be retrieved 15 min later. The amnesia could be overcome by retention-testing or by a new, related, learning experience before or up to 30 min after onset of amnesia. Control birds injected with saline or lumicolchicine, a biologically inactive derivative of colchicine, showed normal retention. Vinblastine sulphate, which also interrupts microtubular networks and hence axonal flow, had no amnesic properties. Colchicine injections had no effect on the levels of acetylcholinesterase, choline acetyltransferase, glutamic acid decarboxylase, and muscarinic acetylcholine receptors in the whole forebrain or in forebrain synaptosomes during the amnesic period. Nor did colchicine injections affect amino acid uptake and protein or glycoprotein synthesis before or during the amnesic period, although there was 10-20% inhibition of protein synthesis 5 h after injection. Thus over the amnesic period, there was no evidence of gross perturbation of brain function. Electron microscopy showed microtubules intact within 1 mm of the injection site 2.5 after injection. Oedema was found at this time in chicks injected with a high dose (100 micrograms) shown to disturb behaviour grossly, but not with a low dose (5 micrograms) which caused amnesia. Transient amnesia for one-trial avoidance learning is most probably caused by secondary effects of colchicine on nerve cell function. We suggest that the amnesic episode represents destruction of one of the stages of a multiple independent parallel process of memory consolidation.
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PMID:The effects of colchicine and vinblastine on memory in chicks. 616 77

A Silastic nerve cuff containing colchicine (1% w/v) was placed around the combined lingualchorda tympani nerve of the Mongolian gerbil (Meriones unguiculatus) to evaluate the role of axonal transport in the maintenance of taste buds. After 3 days the summated gustatory impulse discharges recorded from the chorda tympani nerve were reduced by 60%, while compound action potentials had not changed appreciably. The lingual-chorda tympani nerve underwent ultrastructural changes including a loss of microtubules, an increased prominence and disorientation of neurofilaments, and a significant shrinkage in the cross-sectional area of axoplasm. The shrinkage of axoplasm and the accumulation of mitochondria and cholinesterase at the nerve cuff provided evidence that the colchicine treatment acted to impair axonal transport. More substantial pathological changes were evident in nerve ultrastructure by 15 days when both the ipsilateral chorda tympani taste responses and fungiform taste buds were nearly absent. Control cuffs lacking colchicine had little effect on chorda tympani taste responses, taste buds, or nerve ultrastructure. Eight or 15 days of nerve exposure to lumicolchicine, an isomer of colchicine with low affinity for tubulin, had no significant effect on taste responses. [3H]Colchicine was used in the nerve cuff to demonstrate that colchicine must have acted directly upon the nerve trunk, rather than the taste buds, to cause the loss of taste responses and taste buds. [3H]Colchicine levels were equal in the two sides of the tongue, whereas both the functional and structural deterioration of the taste buds were restricted to the ipsilateral side. We conclude that the loss of taste responses and taste buds was caused by chronically impaired axonal transport in gustatory axons.
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PMID:Chronic impairment of axonal transport eliminates taste responses and taste buds. 618 53

Colchicine (5-10 microM) increased choline acetyltransferase (ChAT) activity 5-10-fold and suppressed acetylcholinesterase (AChE) and glutamate decarboxylase (GAD) activities to 30% and 50%, respectively, of the levels of control cells in mouse spinal cord cells cultured for several days. The synthesis of radiolabeled acetylcholine (ACh) from [14C]choline was also enhanced 4.6-fold, although the uptake of [14C]choline into cells was decreased to 80% of control level. Neither the incorporation of [3H]leucine into protein nor the total amount of protein was increased by colchicine. Vinblastine also increased ChAT activity while cytochalasin B was not effective. Immunochemical titration study revealed that the increase of ChAT activity by colchicine was due to the accumulation of ChAT molecules. Co-culture of spinal cord cells with skeletal muscle markedly stimulated ChAT activity, and the addition of colchicine to the cocultures showed greater than additive effect. These observations indicate that colchicine increases ChAT molecules in a specific manner, that the stimulatory effect of colchicine on ChAT activity is possibly mediated via the interaction with microtubules, and that the increase of ChAT activity is based on a mechanism different from that of co-cultures with skeletal muscle cells.
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PMID:Increase of choline acetyltransferase by colchicine in primary cell cultures of spinal cord. 672 56

Direct infusion of colchicine into the dentate gyrus of the hippocampus kills granule cells and elicits behavioral, neurochemical and neuroanatomical changes. Colchicine-treated rats are less sensitive to the behavioral effects of cholinergic muscarinic receptor antagonists and more sensitive to cholinergic agonists. These behavioral changes are associated with time- and dose-dependent alterations in the cholinergic signal transduction mechanism. Carbachol-stimulated turnover of phosphoinositides is increased in the hippocampus of colchicine-treated rats; similar changes are not observed in the cortex or striatum of colchicine-treated animals. Intradentate colchicine produces a significant increase in choline- acetyltransferase activity and staining for acetylcholinesterase activity in the hippocampus, suggesting reactive synaptogenesis of cholinergic fibers. Other studies have shown that the integrity of the septohippocampal pathway is necessary for these colchicine-induced compensatory changes to occur. It is suggested that the mechanism for these neurochemical changes in colchicine-treated animals may be occurring via alterations in negative feedback control of receptor-G-protein-mediated phosphoinositide hydrolysis.
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PMID:Compensatory changes in the hippocampus following intradentate infusion of colchicine. 785 85

Intracerebroventricular (i.c.v.) administration of colchicine, a microtubule-disrupting agent, causes cognitive dysfunction and oxidative stress. The present study was designed to investigate the protective effects of quercetin against colchicine-induced memory impairment and oxidative damage in rats. An i.c.v. cannula was implanted in the lateral ventricle of male Wistar rats. Colchicine was administered at dose of 15 microg/rat. Morris water maze and plus-maze performance tests were used to assess memory tasks. Various biochemical parameters such as lipid peroxidation, reduced glutathione, nitrite level, acetylcholinesterase and proteins were also assessed. Central administration of colchicine (15 microg/rat) showed poor retention of memory. Chronic treatment with quercetin (20 and 40 mg/kg, p.o.) twice daily for a period of 25 days beginning 4 days prior to colchicine injection significantly improved the colchicine-induced cognitive impairment. Biochemical analysis revealed that i.c.v. colchicine injection significantly increased lipid peroxidation, nitrite and depleted reduced glutathione activity in the brains of rats. Chronic administration of quercetin significantly attenuated elevated lipid peroxidation and restored the depleted reduced glutathione, acetylcholinesterase activity and nitrite activity. The results of the present study clearly indicated that quercetin has a neuroprotective effect against colchicine-induced cognitive dysfunctions and oxidative damage. This article was published online on 3 November 2008. An error was subsequently identified. This notice is included in the online and print version to indicate that both have been corrected.
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PMID:Protective effect of quercetin against ICV colchicine-induced cognitive dysfunctions and oxidative damage in rats. 1898 Feb 5


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