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)

Using choline acetyltransferase (ChAT) immunocytochemistry and acetylcholinesterase (AChE) histochemistry, we investigated regional and laminar differences in cholinergic innervation in the cerebral cortex, hippocampus, amygdala, and thalamus of mice. In mice, unlike rats, the patterns of ChAT-immunostained and AChE-positive fibers are virtually identical in the cortex and are organized in a trilaminar pattern with cholinergic processes prominent in layers I and IV and within the lower portion of layer V and upper segment of layer VI. ChAT-immunoreactive cells were not seen in cortex. In the amygdala, the basolateral nucleus showed the highest density of cholinergic processes. In the hippocampus, a thin, dense band of ChAT-labeled processes was present in the inner segment of the molecular layer of the dentate gyrus and within the stratum oriens of CA1-3, adjacent to the basal aspect of pyramidal cells. Within the thalamus, anteroventral, mediodorsal (lateral portion), intralaminar, and reticular nuclei showed high densities of cholinergic processes. The results of this study provide the basis for examining the effects of transgenes and age on forebrain cholinergic systems.
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PMID:Cholinergic innervation of mouse forebrain structures. 800 18

The changes in extracellular gamma-aminobutyric acid (GABA) levels, the modifications in binding capacities of GABA-receptor subtypes A and B and of the Cl- ionophore sites localized in the ionic-channel associated to the GABAA receptors were studied in hippocampus of rats subjected to a convulsive dose of the acetylcholinesterase inhibitor soman. Whereas extracellular GABA levels, just as binding on GABAA and GABAB receptors, were not modified under soman, a significant transient decrease in the binding capacities of the Cl- ionophore site of the GABAA receptor complex occurred within the first 10 min of seizures in CA1, CA3 areas, and in the dentate gyrus with return to basal values after 30 min. Accordingly, a transient decrease of the brain muscimol-gated Cl- influx was observed after 10 min of seizures. An increased ability of diazepam to potentiate the GABAA gated Cl- influx occurred at the same time. Altogether, these data demonstrated that an impairment of the GABAA receptor function occurs at the beginning of seizures. This suggests that a temporary decrease of GABAAergic function may contribute to the onset of seizures.
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PMID:Transient impairment of the gabaergic function during initiation of soman-induced seizures. 811 28

The effects of pre-treatment with ENA-713, an acetylcholinesterase (AChE) inhibitor, on changes in pre- and postsynaptic cholinergic indices in gerbil brain following transient ischemia were studied at 4 and 14 days after recirculation. In the ischemic group, hippocampal acetylcholine (ACh) level was significantly reduced (to 23% of sham-operated controls) at 4 days post-ischemia, but this reduction was completely prevented by ENA-713 treatment. Choline acetyltransferase (ChAT) and cholinesterase (ChE) activities were not significantly changed at 4 and 14 days post-ischemia. Although the maximum number (Bmax) of muscarinic ACh receptor (mACh-R) binding in the hippocampus was decreased (to 44%) without any change in affinity at 14 days post-ischemia, this decrease was also inhibited by ENA-713 treatment. In addition, histological experiment indicated that ENA-713 inhibited ischemia-induced pyramidal cell loss in the hippocampal CA1 regions. Thus, these findings suggest that ENA-713 has protective, neurotrophic and therapeutic effects on cerebrovascular type dementia due to cerebral ischemia.
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PMID:Acetylcholinesterase inhibitor ENA-713 protects against ischemia-induced decrease in pre- and postsynaptic cholinergic indices in the gerbil brain following transient ischemia. 818 20

Fetal hippocampal neurons were stereotaxically transplanted to five-day-old ischemic CA1 lesions in adult rat hippocampi. The recipient brains were examined 14 or 100 days later. The grafts survived well, and transplanted cells usually formed clusters in the host CA1 subfield. In vitro receptor autoradiography was employed to map the following receptors, the ligands indicated in parentheses being used for labeling: muscarinic cholinergic ([3H]quinuclidinyl benzilate), adenosine A1 ([3H]cyclohexyladenosine), kainate ([3H]kainic acid), spirodecanone ([3H]spiperone), opioid ([3H]naloxone), and GABAA ([3H]muscimol). The receptor autoradiographic technique showed significant binding of the six ligands in all hippocampal grafts two weeks after transplantation. One hundred days following transplantation, almost all receptors, especially muscarinic cholinergic, adenosine A1 and opioid receptor bindings in grafts, had significantly increased compared to bindings two weeks after transplantation. At this time, kainate and muscarinic cholinergic receptors in grafts had increased up to the near normal level of the CA1 in the hippocampus. Interestingly, adenosine A1 receptors in the grafted side had significantly increased not only in the CA1 but also in the stratum oriens of the CA3 compared with that in the non-grafted side. The increase of [3H]quinuclidinyl benzilate binding corresponded well with the innervation of acetylcholinesterase-positive fibers at 100 days after grafting. These results demonstrate that the transplanted neurons, which showed both pre- and post-synaptic autoradiographic markers in the ischemic CA1 lesions, are able to develop their properties and express the nature of normal hippocampal neurons.
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PMID:Neural grafting to ischemic CA1 lesions in the rat hippocampus: an autoradiographic study. 824 65

Numerous reports have indicated that nerve growth factor (NGF) exerts neurotrophic effects on the cholinergic neurons of the basal forebrain. Receptors for NGF (NGFR) have been demonstrated on cholinergic perikarya in the medial septum, diagonal band of Broca, and basal nucleus of Meynert. These neurons provide the major cholinergic innervation to the cerebral cortex and hippocampus, and previous studies have shown that their terminal plexuses also possess NGFR. However, these studies have shown only isolated examples of immunoreactive fibers. In the present paper we confirm and extend the observation of the presence of NGFR immunoreactivity in the hippocampus and cortex of adult rat by showing the entire plexus and demonstrating that the plexus is strikingly similar to the pattern of cholinergic innervation. Fibers stained for acetylcholinesterase (AChE) and NGFR immunoreactivity were found in all layers of the parietal cortex. Within the hippocampus, fibers were observed in all regions, but were most dense in the strata oriens, pyramidale, and radiatum of hippocampal subfields CA1 and CA3. Particularly intense staining was found throughout the dentate gyrus. Partial transections of the fimbria-fornix, which disrupt fibers projecting from the medial septum to the hippocampus, concomitantly abolish the innervation pattern of both NGFR and AChE. These results provide additional evidence that NGFR are associated with septohippocampal and basocortical cholinergic fibers.
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PMID:Fibers immunoreactive for nerve growth factor receptor in adult rat cortex and hippocampus mimic the innervation pattern of AChE-positive fibers. 827 31

The effects of the irreversible acetylcholinesterase (AChE) antagonist paraoxon (Px) on hippocampal neurophysiology were investigated and compared to those of physostigmine in urethane-anaesthetized rabbits. Hippocampal CA1 EEG signals were analyzed by power spectra. Following intracarotid administration, the two drugs induced a similar fundamental low-frequency theta power peak while the appearance of a second theta harmonic was commonly found under Px. Again, inhibition of CA1 pyramidal cells firing was significantly more pronounced after Px injection than after physostigmine. A potent inhibitory action was also described following local Px iontophoretic application. However, a discrepancy appeared between the effects of Px and the classical cholinergic drugs (acetylcholine, physostigmine). The results indicate that Px and physostigmine have a rather similar influence on the septo-hippocampal pathway and support suggestions that Px could act within local hippocampal circuitry through other systems than the cholinergic system exclusively.
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PMID:Effects of organophosphates on rabbit pyramidal cells firing pattern and hippocampal theta rhythm. 829 9

The vulnerability of the human hippocampal complex to disease, trauma, and aging indicates the necessity to target this area therapeutically. The distribution and density of transmitter receptors provide a rational basis for this approach, and in this study the topography of 11 different pharmacological sites is compared with the cholinergic innervation, which is particularly vulnerable in dementia. The regional distribution of cholinergic innervation to the normal adult human hippocampus and adjacent cortex, marked by acetylcholinesterase (AChE) fiber and terminal reactivity, is notable for its concentration in CA2/3 of Ammon's horn and the dentate fascia. Neither nicotinic (high-affinity nicotine binding) nor muscarinic ("M1" or "M2") cholinergic receptor binding paralleled this distribution. In Ammon's horn, 5-HT2 and kainate receptor binding more closely resembled the pattern of AChE, being concentrated in CA2-4 compared with CA1. By contrast, muscarinic M1 and M2, 5-HT1A, benzodiazepine (including zolpidem-insensitive binding), NMDA (MK801), and AMPA/QUIS receptors were higher in CA1 and/or subiculum. Kainate binding, like AChE, was high in CA4. 5-HT2 and nicotinic binding partially mimicked the pattern of AChE around the granule layer. In the subicular complex and parahippocampal gyrus, where cholinergic activity is relatively lower, muscarinic, 5-HT1A, and benzodiazepine binding were relatively high and the nicotinic receptor was remarkable for its highest density compared to other areas examined. In stratum lacunosum-moleculare of CA1, which was relatively low in AChE activity, there was a dense band of nicotinic, M2, and benzodiazepine receptor binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autoradiographic comparison of cholinergic and other transmitter receptors in the normal human hippocampus. 839 72

The effects of ibotenic acid induced lesions of the dentate gyrus on hippocampal glucose utilization and parvalbumin-positive neurons were evaluated in male Wistar rats. Ibotenic acid was injected in the right dorsal dentate gyrus. Quantification of glucose utilization was performed 3 days, 3 weeks, or 3 months after the lesion using the 14C-2-deoxyglucose method. Nissl-stained sections and sections stained for acetylcholinesterase were used as references for anatomical delineation of the hippocampal cytoarchitecture. Additional sections were stained for parvalbumin. The results revealed widespread reductions of glucose utilization in all layers and sectors of the hippocampus in the ipsilateral lesioned hemisphere and also in the nonlesioned contralateral hemisphere. The reductions occurred as early as 3 days after the lesion and persisted up to 3 months. In neither hippocampal structure did glucose utilization return to control levels. Immunohistochemical visualization of parvalbumin-containing neurons revealed that these putatively inhibitory neurons persisted in the otherwise granule-cell-depleted area. The data show that interruption of the excitatory trisynaptic pathway from the entorhinal cortex to the CA1 at the level of the dentate gyrus affects hippocampal glucose utilization irreversibly and uniformly. Since some inhibitory neurons seem to survive the ibotenic acid lesion, we suggest that the reductions of hippocampal glucose utilization reflect an imbalance in favor of inhibitory neurons in the ipsilateral hippocampus after the lesion, which manifests also in the contralateral hemisphere via the commissural pathways.
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PMID:Time course of hippocampal glucose utilization and persistence of parvalbumin immunoreactive neurons after ibotenic acid-induced lesions of the rat dentate area. 840 23

Compounds possessing neurotrophic properties may represent a possible treatment for neurodegenerative disorders such as Alzheimer's disease. SR 57746A, 1-[2-(naphth-2-yl)ethyl]-4-(3-trifluoromethylphenyl)-1,2,5,6- tetrahydropyridine hydrochloride, is a new compound with neurotrophic activity in a number of in vitro preparations. The neurotrophic effects of this compound have been evaluated in vivo using four distinct rat models of neurodegeneration: transient global ischaemia produced by a four-vessel occlusion; septohippocampal lesion produced by injection of vincristine sulphate into the medial septum; sciatic nerve crushing; and acrylamide-induced peripheral neuropathy. Rats were administered vehicle or 2.5-10 mg/kg p.o. SR 57746A, after initiation of the degenerative process, then once daily for 10 days in the first two models, 16 days in the third and 26 days in the fourth model. Median scores for ischaemia-induced neuronal damage were reduced by 30-40% by SR 57746A treatment in hippocampal CA1, CA2, and CA3 regions, and in the dorsal striatum. Twelve days after intraseptal vincristine administration, there was a marked loss of septohippocampal cholinergic neurons, as indicated by reduced choline acetyltransferase activity in both the septum and hippocampus. SR 57746A dose-dependently reversed this reduction in both areas. These results were confirmed by histoenzymological evaluation of hippocampal acetylcholinesterase content. SR 57746A also reversed the loss of hippocampal choline acetyltransferase induced by intraseptal vincristine in marmosets. Behavioral deficits in these models (exploratory behaviour in the former and short-term social memory in the latter) were also significantly reduced by SR 57746A treatment. In the sciatic crush model, sensorimotor function improved more rapidly in rats treated with 10 mg/kg SR 57746A. In this same model, SR 57746A (10 mg/kg/day) also significantly increased the length of regenerated nerve eight days after the crush, as measured using the pinch test. Finally, SR 57746A retarded the onset, reduced the amplitude and accelerated the recovery of acrylamide-induced peripheral neuropathy. Thus, SR 57746A possesses notable neurotrophic activity in a variety of neurodegenerative models in vivo, suggesting that the compound may possess therapeutic potential for the treatment of neurodegenerative diseases.
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PMID:Protective effects of SR 57746A in central and peripheral models of neurodegenerative disorders in rodents and primates. 841 26

Ontogenic development of muscarinic receptors was examined in the hippocampus of rabbits (from P2 to P60) using radioautographic method. Muscarinic sites were labelled with (3H)-quinuclinidyl-benzilate and pharmacologically defined M1 and M2 receptor subtypes with (3H)-pirenzepine and (3H)-oxotremorine, respectively. The distribution of binding sites was compared to acetylcholinesterase (AChE) staining in adjacent hippocampal sections. The two cholinergic components are progressively set up in the hippocampus during the first three postnatal weeks. The AChE staining was very low in all hippocampal fields in P2 rabbits. At P8 and after, the AChE staining was more pronounced in CA3 and CA4 than in CA1 and CA2. On the contrary, the M1 muscarinic binding sites were more abundant in CA1 and CA2 hippocampal fields than in CA3 and CA4 at all ages studied. M2 muscarinic binding sites were only distinguishable at P45 and have a relatively homogeneous distribution. This study shows a differential developmental evolution in the distribution of AChE and muscarinic M1 receptors, and no obvious correspondence between these two cholinergic markers was observed.
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PMID:Ontogenic distribution of muscarinic receptors and acetylcholinesterase in the rabbit hippocampus. 851 62


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