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)

We have established a primary neuronal cell culture technique from the postnatal (P11 to P15) rat CNS to study the nerve growth factor (NGF) response to basal forebrain cholinergic neurons. The survival of septal cholinergic neurons in culture was monitored both by the determination of choline acetyltransferase activity and by counting acetylcholinesterase-positive cells. Cells obtained from postnatal septal regions were found to require a plentiful oxygen supply during the dissociation of the cells. NGF-mediated survival of the septal cholinergic neurons was similarly observed in the cultures by using different plating cell densities up to 12.5 X 10(5) cells/cm2. These results suggest that the promotion by NGF of cell survival in culture is independent of plating cell density.
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PMID:Nerve-growth-factor-dependent and cell-density-independent survival of septal cholinergic neurons in culture from postnatal rats. 217 Aug 75

Transection of the fimbria-fornix pathway is a paradigm that has been richly exploited in rats to assess the structural and functional correlates of cognitive behavior, neural grafting, and growth factor administration. Principally, the degeneration of cholinergic neurons within the septal/diagonal band region has received detailed attention following this manipulation. In contrast, no studies have examined the response of the cholinergic septal/diagonal neurons following axotomy in nonhuman primates. This study examined the neuronal and glial responses within the septal region to selective fornix transection (without cingulate gyrus ablation) in four Cebus apella monkeys. One month following unilateral transection of the fornix by means of an open microsurgical approach, a comprehensive loss of acetylcholinesterase [AChE]-containing fibers was observed throughout the hippocampal formation and dentate gyrus ipsilateral to the lesion. Decreases in AChE fiber densities were also observed within the entorhinal cortex ipsilateral to the lesion. No such changes in AChE-fiber density were consistently observed within the subicular region. The decrease in hippocampal AChE-positive fibers was paralleled by a 49.5% reduction in cholinergic medial septal neurons as revealed by Nissl stains and immunohistochemical staining for the receptor for nerve growth factor, a marker of cholinergic basal forebrain neurons in primates. In contrast, no significant changes in the number of neurons within the vertical limb of the diagonal band were noted. Following the transection, a relatively intense reactive gliosis was observed within the dorsal half of the septal region ipsilateral to the transection and within the overlying transected corpus callosum. These data provide the foundation in nonhuman primates on which novel therapeutic factors can be evaluated in paradigms relevant to the study of Alzheimer's disease.
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PMID:Response of the monkey cholinergic septohippocampal system to fornix transection: a histochemical and cytochemical analysis. 217 23

In co-cultures of rat septum and hippocampus, cholinergic neurons, identified by immunocytochemical techniques using antibodies against choline acetyltransferase, were found to be exclusively located in septal tissue. The presence of nerve growth factor during the entire growth period of four weeks increased the activities of acetylcholinesterase and choline acetyltransferase about 10-fold and strongly increased the number of acetylcholinesterase-positive neurons. Application of nerve growth factor yielded different effects depending on the age of the cultures. During the first two weeks in vitro, nerve growth factor enhanced the number of acetylcholinesterase-positive neurons, an effect which was no longer observed following later applications of nerve growth factor. Nerve growth factor increased the activities of cholinergic enzymes during all phases of in vitro development, but the effects of one-week applications were always considerably smaller than those observed following continuous application of nerve growth factor. The results of different application schedules suggest that the continuous presence of nerve growth factor is needed for maximal increases in cholinergic enzyme activities and maintenance of cholinergic neurons in septohippocampal co-cultures.
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PMID:Continuous presence of nerve growth factor is required for maintenance of cholinergic septal neurons in organotypic slice cultures. 221 21

Cocultures of septal and hippocampal tissues taken from 6- to 7-day-old rats were maintained in culture for up to 30 days in the presence and absence of nerve growth factor (NGF), and their Chol-1 contents determined at varying time intervals by a modified enzyme-linked immunosorption assay (ELISA). The major brain gangliosides were determined densitometrically after spraying chromatograms with resorcinol reagent. There was little change in the contribution of the major gangliosides to the total ganglioside content of the explants either with time or the presence or absence of NGF, the only exception being an NGF-insensitive fall in the contribution of GM1 to about 60% of its initial value at 20 and 30 days. By contrast, the concentration of Chol-1 expressed either per unit weight of ganglioside sialic acid or protein increased considerably in culture and this increase was enhanced by NGF. The effect of NGF resembles that on other cholinergic markers, choline acetyltransferase and acetylcholinesterase, and may be attributed to an NGF-stimulated hippocampal ingrowth of cholinergic fibres and enhanced survival of cholinergic septal neurons. The Chol-1 concentration finally attained in the presence of NGF and the time course of its increase parallel those previously found in vivo and indicate the potential usefulness of septal-hippocampal cocultures for investigating the function of Chol-1.
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PMID:Nerve growth factor enhances the expression of the cholinergic-specific ganglioside Chol-1 in cocultures of rat septum and hippocampus. 223 Aug 14

Mouse 3T3 fibroblasts were genetically modified by transfection with a mammalian expression vector containing the rat beta-nerve growth factor (NGF) gene. The transfected cell line, designated 3E, contains several hundred copies of the rat NGF gene and secretes high levels of biologically active NGF. Pieces of collagen gel containing the NGF-secreting 3E cells were grafted to the brains of unilaterally fimbria-fornix-lesioned rats. Grafts of the genetically modified NGF-producing cells rescued axotomized basal forebrain cholinergic neurons and significantly reduced cholinergic cell death in the medial septum as compared with rats treated with grafts of the parental 3T3 cells. Grafted fibroblast cells were detected, and rescue effects were noted up to 6 weeks after grafting. Local effects of NGF secreted by grafted cells were also seen at the gel-brain border in the form of sprouting acetylcholinesterase immunoreactive host cortical fibers. We suggest that implantation of genetically modified cells producing NGF may have therapeutic applications in rescuing damaged central cholinergic neurons in senile dementia of the Alzheimer type as well as in providing trophic support for chromaffin tissue grafts in Parkinson's disease.
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PMID:Rescue of basal forebrain cholinergic neurons after implantation of genetically modified cells producing recombinant NGF. 232 66

Recent evidence has demonstrated the presence of nerve growth factor (NGF) in areas of the central nervous system characterized by cholinergic innervation. We report that a unique population of rat basal forebrain magnocellular neurons that project to the cortex and hippocampus are immunoreactive to a monoclonal antibody to the NGF receptor. Removal of target contact results in a time-dependent loss or shrinkage of cells in the basal forebrain that stain for NGF receptor and acetylcholinesterase, suggesting that under normal conditions, basal forebrain cholinergic neurons utilize NGF for trophic support.
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PMID:Basal forebrain magnocellular neurons stain for nerve growth factor receptor: correlation with cholinergic cell bodies and effects of axotomy. 243 25

Slices were prepared from septal and hippocampal tissue and co-cultured for periods up to one month. The presence of cholinergic neurons within the septal slices was demonstrated by histochemical staining techniques for acetylcholinesterase or by Golgi-like immunoperoxidase techniques with antibodies raised against the enzyme choline acetyltransferase. Cholinergic fibers originating in the septal explants started to grow radially in all directions. By day 7, the first fibers were seen to reach their target, but maximal hippocampal ingrowth occurred between day 8 and 14 in vitro. Only those fibers reaching the target were maintained, whereas cholinergic fibers growing in other directions degenerated. Electrophysiological studies showed that cholinergic fibers established functional cholinergic connections with hippocampal pyramidal cells. As a result of septal stimulation, two different potassium currents were inhibited in pyramidal cells: a calcium-independent current, IM, and a calcium-dependent current, IAHP, underlying spike afterhyperpolarization. Application of nerve growth factor (NGF) strongly increased the number of cholinergic fibers which invaded the hippocampal slices and raised the activities of the cholinergic enzymes choline acetyltransferase and acetylcholinesterase, effects which were completely blocked by anti-NGF antibodies. The response of septohippocampal co-cultures to NGF depended on the time of application. During the first two weeks in vitro, NGF elicited sustained increases in enzyme activities, whereas later administration of NGF produced effects which were only maintained for several days.
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PMID:Development of the septohippocampal projection in vitro. 253 95

The in vitro and in vivo relevance of basic fibroblast growth factor (bFGF) for rat septal neurons was studied and compared with the effects of nerve growth factor (NGF). Implantation of gel foam soaked with saline, NGF or bFGF following fimbria fornix (FF) transection in adult rats showed that after 4 weeks the neuronal death in the medial septum of saline-treated rats (87% as compared to the unlesioned side) was reduced by NGF- or bFGF-treatment (NGF 0.3 micrograms: 71%; NGF 20 micrograms: 54%; bFGF 8 micrograms: 68%). These results indicate that both NGF and bFGF are able to sustain neurons in the medial septum after FF transection. Moreover, choline acetyltransferase (ChAT)-immunocytochemistry revealed that rescued neurons comprise a large proportion of the cholinergic population. In cultured embryonic rat septal neurons seeded at high densities both NGF and bFGF significantly enhanced ChAT activity (7.5- and 3-fold, respectively) without affecting cell survival. In low density cultures both neurotrophic proteins increased the survival after 4 days. The portions of cholinergic and GABAergic neurons did not change after NGF- and bFGF-treatment (acetylcholinesterase cytochemistry, anti-GABA immunocytochemistry). These results show that i) NGF and bFGF promote survival of embryonic septal cholinergic and GABAergic neurons and may enhance ChAT activity, and ii) bFGF is a potent trophic factor for septal neurons in vivo and in vitro.
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PMID:A role of basic fibroblast growth factor for rat septal neurons. 253 96

A monoclonal antibody raised against the receptor for nerve growth factor (NGF) has been used to map the distribution of NGF receptor-containing profiles within the human basal forebrain of four male and three female elderly patients without neurologic or psychiatric illness. Immunohistochemically processed tissue reveals a continuum of NGF receptor-positive neurons located within the medial septum, vertical and horizontal limb nuclei of the diagonal band, and nucleus basalis. NGF receptor-containing neurons are also found within the bed nucleus of the stria terminalis, the anterior commissure, the internal capsule, and the internal and external medullary laminae of the globus pallidus. Virtually all (greater than 95%) NGF receptor-containing neurons colocalize with the specific cholinergic marker choline acetyltransferase (ChAT) or the nonspecific marker acetylcholinesterase (AChE). Conversely, a few cholinergic perikarya are found which are not NGF receptor positive (and vice versa). These findings demonstrate that human basal forebrain neurons on which NGF receptor immunoreactivity is detected are primarily cholinergic and analogous to the nonhuman primate Ch1-Ch4 subgroups of Mesulam et al. (J. Comp. Neurol., 214:170-197, '83). NGF receptor-containing fiber tracts are observed emanating from the medial septum and vertical limb nucleus of the diagonal band coursing medially within the fornix. Another fascicle originating mainly from the nucleus basalis and travelling within the external capsule enroute to the cortex is observed innervating all cortical layers. Comparison of NGF receptor- and ChAT-containing neurons reveals cholinergic perikarya within the striatal complex, whereas virtually no NGF receptor-containing neurons are found in these structures. An occasional displaced NGF receptor-containing neurons is seen in the ventrolateral portion of the putamen and the white matter underlying the nucleus accumbens. These data are discussed in terms of the relationship of NGF receptor- and ChAT-containing neurons within the basal forebrain and in terms of the possible functional significance of NGF in normal and diseased brain.
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PMID:Nerve growth factor receptor immunoreactive profiles in the normal, aged human basal forebrain: colocalization with cholinergic neurons. 254 49

We report here the possible involvement of a new protease in neurite initiation by PC12h cells. Addition of a leupeptin analogue (Ac-Leu-Leu-Nle-al, ALLNal) to PC12h cells on culture plates coated with collagen type I caused de novo neurite outgrowth. Other protease inhibitors (Ac-Leu-Leu-Met-al, leupeptin, E64c, E64d, soybean trypsin inhibitor, hirudin, aprotinin, diisofluorophosphate, 6-aminocapric acid, and pepstatin A) could not mimic this neurite-initiating action. ALLNal induced the initiation of one or two long neurites from the cell body, and increased the cellular level of acetylcholinesterase to an extent similar to nerve growth factor (NGF). However, ALLNal-induced neuritogenesis is different from that induced by NGF, in which many neurites are induced from a single cell body. In addition, in contrast to neurons induced by NGF, which survive for a long time, ALLNal-induced differentiation was transient, and after 48 h percentage of cells bearing neurites started to decrease. After about 120 h exposure to ALLNal, neurites had mostly disappeared and the acetylcholinesterase activity level was not as great as that produced by NGF. These results provide evidence that ALLNal and NGF elicit neurite initiation by different mechanisms, and suggest the existence of a regulatory system of neuronal differentiation through specific protease-protease inhibitor interaction.
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PMID:The neurite-initiating effect of a tripeptide aldehyde protease inhibitor on PC12h cells. 256 Jul 77


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