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)

Numerous studies suggest that growth and trophic factors play roles in the development and mature function of brain neurons. Recently, growth factors whose actions were previously characterized on non-neuronal cells have been localized to the brain. We sought to determine whether these factors influence septal cholinergic function. Initially, we defined the effects of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) on septal cholinergic cells in dissociated neuronal culture. Both factors elevated activity of the acetylcholine synthetic enzyme, choline acetyltransferase (CAT). To determine whether the factors acted directly on neurons or whether glia mediated the effects, a mitotic inhibitor, 5-fluorodeoxyuridine (FDUR), was added to the cultures to eliminate dividing glia. The action of EGF was completely blocked by the addition of FDUR. However, bFGF elevated CAT activity even in the presence of FDUR. Consequently, bFGF may regulate septal cholinergic function directly, whereas EGF may affect cholinergic cells indirectly through glia. To determine whether increases in CAT activity reflect increased enzyme activity per neuron or an increase in the number of cholinergic cells, bFGF-treated cultures were stained for acetylcholinesterase (AChE) to determine numbers of cholinergic cells. No differences in AChE-positive cells were noted, suggesting that bFGF increased CAT activity per cholinergic neuron. To determine whether bFGF regulates other populations in the septum, we examined GABAergic neurons by monitoring the activity of glutamic acid decarboxylase (GAD), a GABA synthetic enzyme. Basic FGF significantly increased GAD activity; however, the effect was completely abolished by addition of FDUR. Thus, bFGF may act directly on cholinergic neurons and indirectly on GABA cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Septal neuron cholinergic and GABAergic functions: differential regulation by basic fibroblast growth factor and epidermal growth factor. 802 75

Pineal cells of the embryonic quail are multipotent stem cells which are able to differentiate in vitro into pigmented epithelial cells, lens cells and skeletal muscle fibers. Neuronal expression was added in this study in the repertory of differentiating potency of pineal cells. We used immunohistochemical methods to characterize neuronal properties with antibodies against serotonin, GABA, tyrosine hydroxylase and neuron-specific antigen (HPC-1) in addition to the enzyme histochemistry for acetylcholinesterase activity. Cells in the culture were found to be positively stained with these methods, suggesting that embryonic pineal cells are neuropotent to differentiate various types of neuronal cells. We have studied the culture conditions which favor increment of neuronal cells with extension of neuritic processes, and we have found that neuronal cells are maintained for quite a long period under suppressive conditions of DNA synthesis and under the effect of basic fibroblast growth factor (FGF). Suppression of DNA synthesis was achieved by the addition of aphidicolin, an inhibitor of DNA polymerase alpha, in the medium. Time lapse videograph revealed two different cell types participated in neurogenesis; a minor population of small round cells and a major one of flat epithelial cells. Since embryonic quail pineal cells have been shown to differentiate into two types of photoreceptors, the present results show wider retinal potency of cell differentiation by embryonic pineal cells. The cessation of DNA synthesis as well as growth factor(s) may be positively involved in the mechanisms of determination and differentiation of pineal neurons.
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PMID:Retinal differentiation from multipotential pineal cells of the embryonic quail. 813 21

Excitotoxin lesions induced by quinolinic acid (QA) were made unilaterally in the caudate nucleus and putamen of 12 rhesus monkeys. Both acute (2-3 weeks) and chronic (4-6 months) effects were evaluated. Excitotoxin striatal lesions were characterized by a central zone of intense astrogliosis and marked neuronal depletion, which was surrounded by a transition zone in which there was partial neuronal sparing throughout the entire lesioned side. Immunocytochemical and enzyme histochemical markers for both large and medium-sized aspiny- and spiny-striatal neurons clearly demonstrated a selective pattern of neuronal vulnerability to the excitotoxic effects of QA within lesioned striata. Medium-sized spiny neurons containing calbindin Dk28, enkephalin, and substance P were disproportionately lost, while aspiny neuronal subpopulations containing NADPH diaphorase (NADPH-d) and choline acetyltransferase activity (ChAT) were relatively spared. Combined labeling by NADPH-d enzyme histochemistry and Nissl staining, as well as NADPH-d histochemistry and calbindin Dk28 immunocytochemistry, demonstrated significant increases in the ratio of aspiny to spiny neurons within the lesioned striata. Neurochemical measurements confirmed a loss of GABA and substance P-like immunoreactivity yet no significant depletion of somatostatin-like immunoreactivity, neuropeptide Y-like immunoreactivity, or ChAT were seen. The striatal patch-matrix pattern persisted, as demonstrated by acetylcholinesterase activity. The pattern was altered, however, in the chronic animals, such that the matrix zone was significantly reduced, while the total area of patches remained within normal limits. Ultrastructural analysis confirmed axon sparing lesions with neuronal loss and astrogliosis. Pretreatment of 3 monkeys with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, blocked striatal QA neurotoxicity. The present results provide an experimental primate model which closely resembles the neuropathologic and neurochemical features of Huntington's disease. These findings further strengthen the possibility that an NMDA receptor-mediated excitotoxic process plays a role in the pathogenesis of this disorder.
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PMID:Excitotoxin lesions in primates as a model for Huntington's disease: histopathologic and neurochemical characterization. 843 51

Slices of striatal tissue from newborn to eight-day-old rats were cultured for six to 47 days. Cholinergic neurons and fibres were then visualized by histochemical staining for acetylcholinesterase or immunocytochemical staining for choline acetyltransferase. GABA-containing neurons and fibres were visualized by immunocytochemical staining for glutamate decarboxylase or GABA. Corresponding to the normal postnatal development in vivo, acetylcholinesterase staining of the striatal tissue progressed from a "patchy" distribution in the six to 14 days old cultures to an almost even distribution of high acetylcholinesterase activity after 18-27 days. Extrinsic afferents were accordingly not necessary for the maintenance of a patch-matrix-like, acetylcholinesterase distribution during the first one to two weeks in culture, just as a subsequent, normal developmental change of the acetylcholinesterase staining pattern into a more homogeneous distribution also occurred without such afferents. Cholinergic, choline acetyltransferase-immunoreactive neurons were evenly distributed within the cultured striatal tissue, like in vivo, but the density of the neurons appeared to be higher in the cultures. The neurons had a morphology corresponding to the "classical", large-sized, aspiny, cholinergic interneurons in the adult rat striatum. Glutamate decarboxylase-immunoreactive and GABA-immunoreactive neurons were either lightly or darkly stained and of medium size, but some large, lightly stained glutamate decarboxylase-immunoreactive and GABA-immunoreactive neurons were also found. The difference in staining density among the medium-sized cells was observed with both antisera and hence provide evidence for the existence of two populations of medium-sized GABAergic neurons, which in vivo are intensely stained interneurons and more weakly stained, spiny projection neurons. Fibres stained better for glutamate decarboxylase than for GABA and outgrowth of glutamate decarboxylase-immunoreactive nerve fibres from the striatal slice cultures onto the coverslip was often observed. The presence at all culture periods of "protospines" on cell bodies and proximal dendrites of some glutamate decarboxylase-immunoreactive, and in particular some GABA-immunoreactive neurons, suggested that at least some developmental characteristics might be maintained for extended periods in culture. In several cultures, groups of small GABA-immunoreactive cells were observed. Similar groups were also found by staining for glutamate decarboxylase, but a smaller proportion of the cells were then positively stained. In view of their immature appearance with few or no processes, the known presence of GABA in neuroblast-like cells, and the recent demonstration of neuronal and glial progenitor cells in the adult mouse striatum, the small cells might belong to a population of undifferentiated cells surviving in the slice cultures.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Organotypic slice cultures of the rat striatum--I. A histochemical and immunocytochemical study of acetylcholinesterase, choline acetyltransferase, glutamate decarboxylase and GABA. 848 50

The expression of neurochemical phenotypes was studied in long-term cultures of dissociated embryonic neurons from rat hypothalamus. With time in culture, these neurons establish a complex dendritic and axonal network, as indicated by staining with antibodies against microtubulin-associated protein (MAP2) and neurofilaments (SMI32 and SMI33) as well as GABA and glutamate decarboxylase mRNA immunoreactivity. Neurons expressing neuropeptide Y (NPY) mRNA and NPY peptide and opioid-like peptides as well as vasopressin were observed. Further, weakly acetylcholinesterase- and NADPH diaphorase (nitric-oxide synthase)-labelled neurons were present. In conclusion, the neurochemical phenotypes reported for hypothalamic neurons in vivo can be observed in these cultures. This indicates that the culture conditions allow morphological and molecular differentiation. These findings support the view that long-term hypothalamic cultures provide a valuable model for studying mechanisms of neurosecretion in hypothalamic networks.
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PMID:Characterization of neurochemical phenotypes in cultured hypothalamic neurons with immunohistochemistry and in situ hybridization. 851 49

To study the effect of reduced cortical cholinergic activity on GABAergic and glutamatergic mechanisms in cholinoceptive cortical target regions a novel cholinergic immunotoxin (conjugate of the monoclonal antibody 192IgG against the low-affinity nerve growth factor receptor with the cytotoxic protein saporin) was applied, which specifically and selectively destroys cholinergic cells in rat basal forebrain nuclei. To correlate the responses to cholinergic immunolesion in cholinoceptive cortical target regions with cholinergic hypoactivity, quantitative receptor autoradiography to measure NMDA, AMPA and kainate glutamate receptor subtypes, GABAA and benzodiazepine receptors as well as choline uptake sites, and histochemistry to estimate acetylcholinesterase activity were performed in adjacent brain sections. One week after a single intraventricular injection of 4 micrograms of 192IgG-saporin, NMDA receptor binding was markedly reduced in cortical regions displaying a reduced activity of acetylcholinesterase and high-affinity choline uptake sites as a consequence of cholinergic lesion, whereas AMPA and kainate binding sites were significantly increased in these regions. Muscimol binding to GABAA receptors was increased in the caudal portions of frontal and parietal cortices as well as occipital and temporal cortex as compared to the corresponding brain regions from vehicle-injected control rats. Binding levels of benzodiazepine receptors were not affected by the lesion in any of the cortical regions studied. The differential changes in glutamate and GABA receptor subtypes following cholinergic immunolesion might be regarded as the consequence of a cortical reorganization compensating for the reduced cholinergic presynaptic input. The data further suggest that presynaptic cortical cholinergic deficits might affect both glutamatergic and GABAergic functions with different intensity and different directions.
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PMID:192IgG-saporin-induced immunotoxic lesions of cholinergic basal forebrain system differentially affect glutamatergic and GABAergic markers in cortical rat brain regions. 857 66

The widespread use of insecticides has amounted to a large scale 'experiment' in natural selection of insects by chemicals of toxicological importance to humans. Specific examples in which the molecular basis of insecticide resistance has been studied in detail are presented here. The biochemical/physiological mechanisms of resistance can be categorized as target site insensitivity, increased metabolic detoxification and sequestration or lowered availability of the toxicant. These are achieved at the molecular level by: point mutations in the ion channel portion of a GABA receptor subunit (cyclodiene insecticides); point mutations in the vicinity of the acetylcholinesterase (AChE) active site (organophosphorus and carbamate insecticide resistance); amplification of esterase genes (organophosphorus and carbamate insecticides); mutations linked genetically to a sodium channel gene (DDT and pyrethroid insecticides); and yet uncharacterized mutations leading to the up-regulation of detoxification enzymes, such as cytochrome P450 and glutathione S-transferases (many classes of insecticides). In several cases, the selection of a precisely homologous mutation has been observed in different insect species.
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PMID:Molecular biology of insecticide resistance. 859 50

Rats trained on a Delayed Matching To Position (DMTP) task displayed mediating behavior during delays to solve the task. Infusion of the cholinergic antagonist scopolamine into the medial Prefrontal Cortex area (mPFC), dose dependently impaired performance independent of delay. These results indicate that scopolamine does not specifically affect working memory. Infusion of the cholinesterase inhibitor physostigmine, muscarinic subtype receptor antagonists, the dopamine (D1) antagonist SCH23390, and of the GABA-A receptor antagonist bicuculline, did not affect performance in the DMTP task. In a post-hoc analysis scopolamine was found to impair discriminability in a delay-dependent manner only in animals that used mediating behavior in the majority of the trials. Furthermore, a time sampling method indicated that scopolamine infusions into the mPFC disrupted mediating behavior during the task. Results suggest that cholinergic systems in the mPFC play a role in directing attention to task relevant behavior.
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PMID:Effects of infusion of cholinergic drugs into the prefrontal cortex area on delayed matching to position performance in the rat. 868 Aug 52

1. The effects of benzodiazepine receptor (BZR) agonist were investigated in dissociated rat neostriatal neurones by a conventional whole-cell patch recording configuration at room temperature. 2. The dissociated neurones, with a longest somatic diameter of larger than 25 microns, were classified as 'large neurones', while those having soma measuring less than 15 microns were described as 'small neurones'. Large neurones were intensely positive for acetylcholinesterase staining, whereas the small ones were not. 3. CL218,872 enhanced the GABA response in both the large and small neurones with similar EC50S. However, the potentiation efficacy of CL218,872 in large neurones was larger than that of small ones. 4. Zolpidem also potentiated the GABA response in both neuronal populations with similar EC50S. This compound also enhanced the GABA response more strongly in large neurones than in small ones. 5. Zopiclone exerted a prominent potentiation in large neurones, although no difference was seen in the EC50S in the large and small neurones. 6. It was concluded that the BZR in large neurones had a different pharmacological property from that in small ones and that the BZR agonists showed a prominent difference, not in EC50, but in the potentiation efficacy between these neuronal populations.
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PMID:Heterogeneous distribution of benzodiazepine receptors among rat neostriatal neurones. 876 13

Glial cell line-derived neurotrophic factor (GDNF) is a member of the TGF-beta superfamily of growth factors with marked neurotrophic activity on midbrain dopaminergic neurons. To investigate whether this trophic activity is shared by central cholinergic neurons, we investigated the effects of GDNF treatment during development of the medial septal area in rats. Adult Fischer 344 rats received intraocular transplants of fetal septal forebrain tissue (embryonic Day 17) which was preincubated for 20 min with either GDNF or vehicle. The two treatment groups subsequently received weekly intraocular injections of either GDNF (0.5 microgram in 5 microliters/injection) or vehicle for 6 weeks following transplantation. Transplants treated with GDNF grew twice as large as control grafts treated with vehicle. Immunohistochemical evaluations of the transplants revealed that there was no difference between the two groups in terms of acetylcholinesterase or low affinity neurotrophin receptor (p75) staining. In contrast, a significant increment in the number of GABA-ergic neurons was observed in transplants that received GDNF, as compared to vehicle-treated grafts. The overall number of neurons within the transplanted tissue was also elevated in the experimental group. There was no difference between the two groups in the distribution or density of astrocytes in the grafted tissue, as evidenced by immunohistochemistry with antibodies directed against glial fibrillary acidic protein. These results indicate that basal forebrain GABA-ergic neurons may be dependent on GDNF for their survival and/or for GABA synthesis, but that the cholinergic neurons in this area appear to be unaffected by GDNF administration during development.
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PMID:Effects of GDNF on fetal septal forebrain transplants in oculo. 881 51


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