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 origin of the cholinergic innervation to the amygdaloid complex was investigated with the use of acetylcholinesterase (AChE) histochemistry and choline acetyltransferase (ChAT) assay of microdissected nuclei. Visualization of AChE-positive neurones in the ventral forebrain was facilitated by pretreatment of rats with 1.5 mg/kg di-isopropyl phosphofluoridate (DFP). The AChE-positive neurones in the ventral forebrain are distributed in a continuous system from the septum through the lateral preoptic area to the entopeduncular nucleus caudally. Knife cuts or kainic acid injections (1.5 microgram/l microliter) placed in the lateral preoptic area resulted in substantial depletion of the AChE and ChAT content of the amygdala nuclei. Kainic acid injections (1.5 microgram/l microliter) in the diagonal band area or cuts through the stria terminalis dorsally did not significantly modify the AChE staining or ChAT content of the amygdala (although diagonal band injections partially depleted the hippocampus of ChAT). Knife cuts severing both the so-called ventral pathway and the stria terminalis did not produce significantly greater ChAT depletion in the amygdala than those produced by the knife cuts or kainic acid injections in the lateral preoptic area. Parasagittal knife cuts undercutting the lateral pyriform cortex also failed to modify the AChE or ChAT content of the amygdala, but they depleted the undercut cortex of both ChAT and AChE; AChE-positive material accumulated ventrally and medially to the knife cut. It is suggested that the major source of the cholinergic innervation of the amygdala is the magnocellular AChE-positive neurones in the lateral preoptic area and adjacent regions of the ventral forebrain.
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PMID:Choline acetyltransferase and acetylcholinesterase containing projections from the basal forebrain to the amygdaloid complex of the rat. 31 Dec 37

The present experiments were performed to determine whether the age-related loss of striatal D2 receptors could be localized to a kainic acid-sensitive neuronal population. This neurotoxin selectively destroys intrinsic neurons. Thus, if kainic acid reduced striatal D2 receptor concentrations such that age differences in this parameter were no longer observed, it would be a good indication that the D2 receptors lost through aging are also sensitive to kainic acid. Mature (6 months) and senescent (24 months) rats were stereotaxically, unilaterally injected with 3 micrograms/0.5 microliter kainic acid into the right striatum. Seven days later striatal D2 receptors were assessed with [3H]-spiperone in one group of mature and senescent rats. A second group of mature and senescent unilaterally lesioned rats was anesthetized and perfused. Brains were dissected and processed for striatal cell counts using cresyl violet staining, tyrosine hydroxylase and met-enkephalin using immunocytochemistry, and acetylcholinesterase using histochemistry. Age-related differences in D2-receptor concentrations were observed in intact, but not lesioned, striata. Kainic acid was less effective in reducing D2-receptor concentrations in senescent animals, suggesting that some proportion of the receptors was already lost prior to lesioning. Kainic acid also reduced total neuronal numbers, as well as Met-Enk and AChE positive staining, to approximately the same extent in mature and senescent rats. No age differences were seen in any of the other parameters following kainic acid administration.
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PMID:The deleterious effects of aging and kainic acid may be selective for similar striatal neuronal populations. 168 53

Three days after systemic administration of kainic acid (15 mg/kg, s.c.), selected cholinergic markers (choline acetyltransferase, acetylcholinesterase, muscarinic acetylcholine receptor, and high-affinity choline uptake) and GABAergic parameters [benzodiazepine and gamma-aminobutyric acid (GABA) receptors] were studied in the frontal and piriform cortex, dorsal hippocampus, amygdaloid complex, and nucleus basalis. Kainic acid treatment resulted in a significant reduction of choline acetyltransferase activity in the piriform cortex (by 20%), amygdala (by 19%), and nucleus basalis (by 31%) in comparison with vehicle-injected control rats. A lower activity of acetylcholinesterase was also determined in the piriform cortex following parenteral kainic acid administration. [3H]Quinuclidinyl benzilate binding to muscarinic acetylcholine receptors was significantly decreased in the piriform cortex (by 33%), amygdala (by 39%), and nucleus basalis (by 33%) in the group treated with kainic acid, whereas such binding in the hippocampus and frontal cortex was not affected by kainic acid. Sodium-dependent high-affinity choline uptake into cholinergic nerve terminals was decreased in the piriform cortex (by 25%) and amygdala (by 24%) after kainic acid treatment. In contrast, [3H]flunitrazepam binding to benzodiazepine receptors and [3H]muscimol binding to GABA receptors were not affected 3 days after parenteral kainic acid application in any of the brain regions studied. The data indicate that kainic acid-induced limbic seizures result in a loss of cholinergic cells in the nucleus basalis that is paralleled by degeneration of cholinergic fibers and cholinoceptive structures in the piriform cortex and amygdala, a finding emphasizing the important role of cholinergic mechanisms in generating and/or maintaining seizure activity.
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PMID:Changes in cholinergic but not in GABAergic markers in amygdala, piriform cortex, and nucleus basalis of the rat brain following systemic administration of kainic acid. 254 59

Kainic acid was injected bilaterally (4.8 micrograms in 1.2 microliter each side) into the dorsolateral pontomesencephalic tegmentum of cats in order to destroy cholinergic cells which are located within the pedunculopontine tegmental (PPT), laterodorsal tegmental (LDT), parabrachial (PB), and locus ceruleus (LC) nuclei in this species. The neurotoxic lesions resulted in the destruction of the majority (approximately 60%) of choline acetyltransferase (ChAT)-immunoreactive neurons and a minority (approximately 35%) of tyrosine hydroxylase (TH)-immunoreactive neurons, as well as in the destruction of other chemically unidentified neurons, in the region. The effects of these lesions upon the cholinergic innervation of the brain were investigated by comparison of brains with and without lesions which were processed for acetylcholinesterase (AChE) silver, copper thiocholine histochemistry and ChAT radio-immunohistochemistry. In the forebrain, a major and significant decrease in AChE staining, measured by microdensitometry, and associated with a decrease in ChAT immunoreactivity was found in certain thalamic nuclei, including the dorsal lateral geniculate, lateral posterior, pulvinar, intralaminar, mediodorsal and reticular nuclei. All of these nuclei receive a rich cholinergic innervation evident in both AChE histochemistry and ChAT immunohistochemistry. No significant difference in AChE staining or ChAT immunoreactivity was detected in other thalamic nuclei or in the subthalamus, hypothalamus or basal forebrain. In the brainstem, a significant decrease of AChE staining and ChAT immunoreactivity was found in the superior colliculus and the medullary reticular formation, where ChAT-immunoreactive fibers were moderately dense in the normal animal. These results indicate that the pontomesencephalic cholinergic neurons may influence the forebrain by major projections to the thalamus, involving both relay and non-specific thalamocortical projection systems, and thus act as an integral component of the ascending reticular system. They may influence the brainstem by projections onto deep tectal neurons and other reticular neurons, notably those in the medullary reticular formation, and thus also affect bulbar and bulbospinal systems.
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PMID:Neurotoxic lesions of the dorsolateral pontomesencephalic tegmentum-cholinergic cell area in the cat. I. Effects upon the cholinergic innervation of the brain. 325 79

It is well established that the putative excitatory neurotransmitters, glutamate (Glu) and aspartate (Asp), are neurotoxins that have the potential of destroying central neurons by an excitatory mechanism. Kainic acid (KA), a rigid structural analog of Glu, powerfully reproduces the excitatory neurotoxic (excitotoxic) action of Glu on central neurons and, in addition, causes sustained limbic seizures and a pattern of seizure-linked brain damage in rats that closely resembles that observed in human epilepsy. In the course of studying the seizure-related brain damage syndrome induced by KA, we observed that a similar type of brain damage occurs as a consequence of sustained seizure activity induced by any of a variety of methods. These included intraamygdaloid or supradural administration of known convulsants such as bicuculline, picrotoxin and folic acid, or systemic administration of lithium and cholinergic agonists or cholinesterase inhibitors that have not commonly been viewed as convulsants. We have further observed that this type of brain damage can be reproduced in the hippocampus by persistent electrical stimulation of the perforant path, a major excitatory input to the hippocampus that is thought to use Glu as transmitter. It is a common feature of all such neurotoxic processes that the acute cytopathology resembles the excitotoxic type of damage induced by Glu or Asp, which is acute swelling of dendrites and vacuolar degeneration of neuronal soma, without acute changes in axons or axon terminals. We have found that the seizure-brain damage syndrome induced by cholinergic agents can be prevented by pretreatment with atropine and that the syndrome induced by any of the above methods, cholinergic or noncholinergic, can be either prevented or aborted respectively by either pre-or posttreatment with diazepam. Our findings in experimental animals may be summarized in terms of their potential relevance to human epilepsy as follows. Sustained complex partial seizure activity consistently results in cellular damage if allowed to continue for longer than 1 hr. Hippocampal, or Ammon's horn, sclerosis is the primary pathological result. It may be a priority goal, therefore, in the management of human epilepsy to control such seizure activity within very narrow limits. This proposal is discussed in terms of three major transmitter systems that may be involved; cholinergic, GABAergic, and glutamergic/aspartergic. The cholinergic system may play a role in generating or maintaining this type of seizure activity, and anticholinergics may protect against it provided they are given prior to commencement of behavioral seizures.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Excitotoxic mechanisms of epileptic brain damage. 370 27

The cholinergic innervation of the rat's posterior cingulate cortex (Brodmann's area 29) was studied using acetylcholinesterase (AChE) histochemistry. Electrolytic lesion of the ipsilateral medial septum and diagonal band region (MS-DB) reduced the diffuse AChE staining in layers I, II, III and V of the cingulate cortex. Kainic acid lesion of the ipsilateral globus pallidus and substantia innominata area (GP-SI) abolished the dense band of AChE stain in layer IV, with small reductions of AChE stain in other layers. The results indicate that the medial cholinergic pathway from MS-DB terminates diffusely in layers I, II, III and V while the lateral cholinergic pathway from the GP-SI predominantly ends in layer IV of the posterior cingulate cortex.
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PMID:Topographical projection of cholinergic neurons in the basal forebrain to the cingulate cortex in the rat. 407 31

Kainic acid neurotoxicity has been studied in the optic tectum of the goldfish 4 weeks after eye enucleation. The effect of drug treatment has been tested with respect to both neurochemical and morphological parameters. The neurotransmitter-related enzymes, choline acetyltransferase, acetylcholinesterase and glutamate decarboxylase, show about 50% decrease in the deafferented tectum 6 days after kainic acid administration. Relevant morphological alterations of the tectal structure can also be noticed at the same stage. The neurotoxic effects of kainic acid in the deafferented optic tectum are therefore quite similar to the effects of previously noticed for the intact optic tectum of normal fish. Control experiments on the effect of optic nerve degeneration by itself on the levels of the neurotransmitter-related enzymes in the optic tectum, have shown no significant decrease in glutamate decarboxylase, a slight decrease in acetylcholinesterase and a more marked drop in choline acetyltransferase. The findings are discussed with reference to some of the hypotheses advanced in order to explain kainic acid neurotoxicity. It is proposed that the neurotoxic effect of kainic acid after removal of specific excitatory afferents, may vary in different nervous centers depending on differences of the remaining extrinsic connections and of the intrinsic neural circuits.
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PMID:Kainic acid neurotoxicity does not depend on intact retinal input in the goldfish optic tectum. 611 19

Systemic injection of quinuclidinyl benzilate partially abolished low voltage fast activity (LVFA) in the neocortex of waking rats, resulting in the appearance of large irregular slow waves during Type 2 behaviors (e.g. immobility, sniffing without head movement, face washing). These slow waves did not occur during Type 1 behavior (e.g. walking, head movement). Atropine sulfate produced a similar effect but it was less potent by a factor of about 12. Injection of kainic acid into the substantia innominata: (a) destroyed local cells which contain acetylcholinesterase (AChE) and reduced AChE staining in the ipsilateral neocortex; and (b) produced large slow waves in the ipsilateral neocortex during Type 2 behavior but not during Type 1 behavior. These slow waves were abolished by systemic injection of pilocarpine. Kainic acid injection into the thalamus produced extensive local cell loss but failed to produce slow waves in the neocortex. The data suggest that the LVFA which is normally present in the neocortex during waking Type 2 behavior is dependent on a cholinergic input to the neocortex from the substantia innominata. The relevance of these findings to Alzheimer's disease is discussed.
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PMID:Cholinergic activation of the electrocorticogram: role of the substantia innominata and effects of atropine and quinuclidinyl benzilate. 650 15

Kainic acid administration into the cerebellar dorsal lobe of the goldfish causes selective degeneration of some neuronal types. Stellate and Golgi neurons are very sensitive to the neurotoxin and undergo rapid degeneration. On the basis of their differential responses to kainic acid, Purkinje cells can be divided in two distinct sub-populations (i.e. sensitive and insensitive neurons). The degenerative changes of the Purkinje neurons are in addition remarkably slow in comparison with the same cells in mammals or with stellate and Golgi neurons in the goldfish. Granule cells, as well as the cerebellar afferent fiber system, are not significantly affected. Six days after kainic acid administration, the level of glutamate decarboxylase in the cerebellar dorsal lobe drops to about 40% of the control value. This result suggests that the neurons sensitive to kainic acid neurotoxicity are, at least in part, GABAergic. Light- and electron-microscopic autoradiography of cerebellar elements selectively accumulating [3H]GABA, supports this idea. Moderate decreases of acetylcholinesterase and protein content were also noticed in the kainic acid-treated cerebellar dorsal lobe.
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PMID:Neurotoxic effect of kainic acid on ultrastructure and GABAergic parameters in the goldfish cerebellum. 717 84

Choline acetyltransferase (CAT) was assayed in the optic tectum of 4 teleost species with different visual powers. The results showed a close relationship between the enzyme levels in the optic tectum and the development of the visual system. In the more visual species, the trout, CAT activity in the optic tectum was about 30-fold higher than in the catfish, whose visual system is much less developed. Two species with intermediate development of the visual system, the goldfish and the tench, showed intermediate levels of CAT activity. Kainic acid treatment caused a significant decrease in both CAT and acetylcholinesterase (AChE) in the goldfish optic tectum. Concomitant histological examination showed, among other effects, the disappearance of most neurons belonging to the pyramidal and fusiform type in the striatum fibrosum and griseum superficiale of the tectum. The comparative and experimental data therefore suggest that the relationship between cholinergic mechanisms and the visual function is, to a significant extent, connected with the presence of intrinsic cholinergic circuits in the optic tectum. The relevance of these findings, also in relation to the problem of the identification of the retino-tectal transmitter, is discussed.
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PMID:Evidence of intrinsic cholinergic circuits in the optic tectum of teleosts. 737 33


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