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 characteristic electroencephalographic patterns within the hippocampus are theta and sharp waves. Septal neurons are believed to play an essential role in the rhythm generation of the theta pattern. The present study examined the physiological consequences of complete and selective damage of septohippocampal cholinergic neurons on hippocampal theta activity in rats. A selective immunotoxin against nerve growth factor receptor bearing cholinergic neurons (192 immunoglobulin G-saporin), [Wiley R. G. et al. (1991) Brain Res. 562, 149-153] was infused into the medial septal area (0.11-0.42 microgram). Hippocampal electrical activity was monitored during trained wheel running, drinking and the paradoxical phase of sleep, as well as following cholinomimetic treatment. A moderate dose of toxin (0.21 microgram) eliminated the septohippocampal cholinergic projection, as evidenced by a near total absence of choline acetyltransferase-immunoreactive neurons in the medial septum and the vertical limb of the diagonal band, and by the absence of acetylcholinesterase-positive fibers in the dorsal hippocampus. In the same rats, parvalbumin immunoreactivity, a reliable marker for septohippocampal GABAergic neurons, [Freund T. F. (1989) Brain Res. 478, 375-381], remained unaltered. In addition, retrograde transport of the tracer fluorogold demonstrated that the parvalbumin cell population preserved its axonal projection to the hippocampus. Following toxin treatment, the power of hippocampal theta, but not its frequency, decreased in a dose-dependent manner. Reduction of theta power occurred between three and seven days after the toxin treatment and remained unaltered thereafter up to eight weeks. A dose which eliminated all septohippocampal cholinergic neurons (0.21 microgram) left a small but significant theta peak in the power spectra during wheel running, paradoxical phase of sleep and intraseptal infusion of carbachol (5 micrograms). Peripheral administration of physostigmine (1 mg/kg) induced only slow (1.5-2.0 Hz) rhythmic waves. No changes were observed in the gamma (50-100 Hz) band. These findings indicate that the integrity of the septohippocampal GABAergic projection is sufficient to maintain some hippocampal theta activity. We hypothesize that cholinergic neurons serve to increase the population phase-locking of septal cells and thereby regulate the magnitude of hippocampal theta.
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PMID:Hippocampal theta activity following selective lesion of the septal cholinergic system. 784 84

Three groups of marmosets were trained to perform a series of visual discrimination tasks in a Wisconsin General Test Apparatus. Two groups then received bilateral lesions of the basal nucleus of Meynert using the excitotoxin N-methyl-D-aspartate and were found to be severely impaired on relearning a visual discrimination first learnt prior to surgery. One lesioned group then received grafts of acetylcholine-rich tissue dissected from the basal forebrain of fetal marmosets. Three months later the marmosets with lesion alone remained impaired on a number of retention and reversal tasks whereas the transplanted animals were no longer significantly impaired. Histological examination of the brains indicated that all lesioned animals had sustained substantial loss of the cholinergic neurons of the basal nucleus of Meynert (assessed by nerve growth factor receptor immunoreactivity) and that the lesion-alone animals showed marked loss of the cholinergic marker acetylcholinesterase in the dorsolateral frontal and parietal cortex. All transplanted animals had surviving graft tissue (visualized by Cresyl Violet staining, dense acetylcholinesterase staining and the presence of a limited number of nerve growth factor receptor-immunoreactive neurons) in the neocortex and 5/6 transplanted animals showed near complete restitution of acetylcholinesterase staining in frontal and parietal cortex. Examination of individual animal data showed that the animal without this restitution performed very poorly. The performance of the remaining transplanted animals was significantly better than that of the animals with lesion alone. There was a significant positive correlation between the degree of acetylcholinesterase staining and good performance on tasks sensitive to frontal lobe damage. These results demonstrate that acetylcholine-rich tissue transplanted into the neocortex of primates with damage to the cholinergic projections to the neocortex can produce substantial restitution of function provided that an appropriate level of interaction between graft and host tissue is achieved.
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PMID:Restoration of cognitive abilities by cholinergic grafts in cortex of monkeys with lesions of the basal nucleus of Meynert. 789 68

The cholinergic innervation of the hippocampal formation is thought to play an important role in memory processes, but its organization in humans has not been described in detail. We studied the cholinergic innervation of the human hippocampal formation by means of immunohistochemistry with polyclonal antisera directed against acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and the low-affinity (p75) nerve growth factor receptor (NGFR). The density of ChAT-like immunoreactive (ChAT-li) fibers differed substantially among the various regions, in general paralleling the pattern of AChE-li staining. One notable exception was the presence of AChE-li cell bodies. In contrast, ChAT immunoreactivity was associated only with fibers and terminals. NGFR-li staining corresponded closely to the ChAT-li fiber pattern. ChAT-li fibers in the CA fields diffusely filled the stratum pyramidale and extended into the stratum oriens and radiatum as well. The highest density was consistently observed in CA4 and CA3 subfields. Staining decreased from CA4 to CA1 and was substantially less dense in the subicular complex. In the entorhinal cortex, the ChAT- and NGFR-li fiber innervation displayed a laminar pattern, most intense over the nests of cells in layer II. There was a trend towards an age-related reduction in the density of ChAT- and AChE-li fibers and terminals. Nonetheless, we also found a surprisingly conserved NGFR-li innervation and the presence of occasional NGFR-li pyramidal cells, providing evidence of a plastic response in the brains of the elderly patients.
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PMID:Cholinergic innervation in the human hippocampal formation including the entorhinal cortex. 792 5

The cholinergic innervation of the rat amygdala was studied immunohistochemically with antibodies against choline acetyltransferase and the low affinity p75 nerve growth factor receptor in normal rats and in rats lesioned with an immunotoxin, 192 IgG-saporin, directed against the p75 nerve growth factor receptor. The density of choline acetyltransferase-positive fibers was high in the nucleus of the lateral olfactory tract, the basolateral nucleus, and the amygdalohippocampal area; medium in the lateral nucleus, the cortical nucleus, the accessory basal nucleus, the periamygdaloid cortex, and the anterior amygdaloid area; and low in the medial and central nuclei. Nerve growth factor receptor-positive fibers were of medium density in the lateral nucleus, the accessory basal nucleus, the cortical nucleus, the anterior amygdaloid area, the periamygdaloid cortex, and the amygdalohippocampal area. The medial nucleus and the central nucleus displayed a low density of nerve growth factor receptor-positive fibers. The basolateral nucleus and the nucleus of the lateral olfactory tract also contained a low density of nerve growth factor receptor-positive fibers even though the two nuclei displayed the highest density of choline acetyltransferase-positive fibers in the amygdala. Injections of 192 IgG-saporin induced a complete loss of cholinergic nerve growth factor receptor-positive neurons in the basal forebrain but spared a subpopulation of nerve growth factor receptor-negative cholinergic neurons in the nucleus basalis-substantia innominata complex. Following 192 IgG-saporin injections, choline acetyltransferase-positive and acetylcholinesterase-positive fibers were essentially unchanged in the nucleus of the lateral olfactory tract and the basolateral nucleus and showed a partial reduction in the remaining nuclei of the amygdaloid complex. Cholinergic fibers emanating from cholinergic cell group 4 neurons reached the amygdala via the stria terminalis and the ventral amygdalofugal pathway. These observations indicate that two amygdaloid nuclei, the nucleus of the lateral olfactory tract and the basolateral nucleus, receive their cholinergic projections predominantly, if not exclusively, from nerve growth factor receptor-negative cholinergic neurons whereas all remaining amygdaloid regions receive fibers from nerve growth factor receptor-negative as well as nerve growth factor receptor-positive cholinergic neurons.
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PMID:Two types of cholinergic projections to the rat amygdala. 807 89

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

To study whether the changes in cortical noradrenergic and serotonergic mechanisms observed in patients with Alzheimer's disease are the consequence of reduced cortical cholinergic activity, a novel colinergic immunotoxin (conjugate of the monoclonal antibody 192IgG against the lower affinity nerve growth factor receptor with the cytotoxic protein saporin, 192IgG-saporin) was used to produce a specific and selective loss of 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 adrenoceptors and 5-hydroxytryptamine (5-HT) receptor subtypes, and histochemistry to estimate acetylcholinesterase activity, were performed in adjacent brain sections. alpha 1-adrenoceptor and 5-HT1A receptor binding were not affected by cholinergic immunolesion in any of the cortical and hippocampal regions studied. However, cholinergic immunolesion resulted in significantly reduced alpha 2- and beta-adrenoceptor as well as 5-HT2A receptor binding in a number of cortical and hippocampal regions displaying a reduced activity of acetylcholinesterase, already detectable seven days after a single injection of 192IgG-saporin and persisting up to three months post lesion without any significant recovery. The data suggest that at least a subpopulation of alpha 2- and beta-adrenoceptor as well 5-HT2A receptor subtype is present on cortical and hippocampal cholinergic terminals originating in the basal forebrain. The lesion-induced receptor changes suggest that the alterations in cortical 5-HT2 receptor binding observed in patients with Alzheimer's disease might be secondary to cholinergic deficits.
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PMID:Basal forebrain cholinergic immunolesion by 192IgG-saporin: evidence for a presynaptic location of subpopulations of alpha 2- and beta-adrenergic as well as 5-HT2A receptors on cortical cholinergic terminals. 923 51

The small magnocellular group located within the rostrolateral extension of the basal forebrain was named and described as the nucleus subputaminalis in the human and chimpanzee brain by Ayala. Analysis of cytoarchitectonic and cytochemical characteristics of this cell group has been largely disregarded in both classical and more current studies. We examined the nucleus subputaminalis in 33 neurologically normal subjects (ranging from 15 weeks of gestation to 71 years-of-age) by using Nissl staining, choline acetyltransferase immunohistochemistry, acetyl cholinesterase histochemistry and nerve growth factor receptor immunocytochemistry. In addition, we applied reduced nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry and calbindin-D28k immunocytochemistry in three neurologically normal subjects. At the most rostrolateral levels we describe the previously poorly characterized component of the lateral (periputaminal) subdivision of the subputaminal nucleus, which may be human specific since it is not described in non-human primates. Moreover, we find the human subputaminal nucleus best developed at the anterointermediate level, which is the part of the basal nucleus that is usually much smaller or missing in monkeys. The location of subputaminal cholinergic neurons within the frontal lobe, the ascension of their fibers through the external capsule towards the inferior frontal gyrus, the larger size of the subputaminal nucleus on the left side at the most rostral and anterointermediate levels and the most protracted development among all magnocellular aggregations within the basal forebrain strongly suggest that they may be connected with the cortical speech area. These findings give rise to many hypotheses about the possible role of the subputaminal nucleus in various neurodegenerative, neurological and psychiatric disorders, particularly Alzheimer's disease and primary progressive aphasia. Therefore, future studies on the basal forebrain should more carefully investigate this part of the basal nucleus.
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PMID:Nucleus subputaminalis (Ayala): the still disregarded magnocellular component of the basal forebrain may be human specific and connected with the cortical speech area. 1005 Dec 18

The low-affinity nerve growth factor receptor (p75(NGFR)) apparently can mediate apoptosis in a variety of cells in vitro and in vivo. Previously, our laboratory suggested that p75(NGFR) induced apoptosis in a subpopulation of cholinergic forebrain neurons during postnatal development, i.e., the number of choline acetyltransferase (ChAT)-positive neurons in a control strain of mice decreased whereas it remained higher in p75(NGFR)-deficient (-/-) mice. Discrepancies with subsequent data sets in our laboratory caused us to thoroughly re-analyze the fate of these cholinergic medial septum and neostriatal neurons in new sets of p75(NGFR) -/- and two DNA control strains of mice during development. Between postnatal day (P)6 and P15 the number of ChAT-positive neurons detected in the medial septum of 129/Sv mice and Balb/c mice increased by approximately 64% and approximately 62%, respectively. This increase is contrary to previous reports from our laboratory and indicative of normal postnatal development (including an increase in ChAT-enzyme) of the cholinergic forebrain neurons. In p75(NGFR) -/- mice the number of ChAT-positive neurons in the medial septum remained constant between P6 and P15 and was approximately 31% and approximately 56% higher at P6 than 129/Sv and Balb/c mice, respectively. At P15 and adulthood, p75(NGFR) -/- mice had similar numbers of cholinergic neurons as control mice. In the developing neostriatum, the number of ChAT-positive neurons increased by approximately 56% between P6 and P15 and did not differ between p75(NGFR) -/- and control mice at any time. Analyses for apoptotic DNA fragmentation (TUNEL labeling) at P8 revealed no differences between p75(NGFR) -/- and control mice in 12 forebrain regions, including the septum and neostriatum. At all times, all mice had similar levels of acetylcholinesterase-positive cholinergic innervation of the molecular layer in the dorsal dentate gyrus. These findings suggest that the p75(NGFR) does not necessarily mediate apoptosis in medial septum or neostriatal cholinergic neurons during the postnatal time period. The discrepant results of the previous study are most likely due to a less rigorous application of criteria for data acquisition, including anatomical boundaries that define the nucleus.
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PMID:p75(NGFR) and cholinergic neurons in the developing forebrain: a re-examination. 1061 6

Cholinergic medial septum neurons express TrkA and p75 nerve growth factor receptor (p75(NGFR)) and interactions between TrkA and p75(NGFR) are necessary for high-affinity binding and signaling of nerve growth factor (NGF) through TrkA. In adult p75(NGFR)-deficient (-/-) mice, retrograde transport of NGF and other neurotrophins by these neurons is greatly reduced, however, these neurons maintain their cholinergic phenotype and size. Reduced transport of NGF has been proposed to play a role in Alzheimer's disease. Here, we investigated whether chronic and long-term absence of p75(NGFR) (and possibly reduced NGF transport and TrkA binding) would affect the cholinergic septohippocampal system during aging in mice. In young (6-8 months), middle aged (12-18 months), and aged (19-23 months) 129/Sv control mice the total number of choline acetyltransferase-positive medial septum neurons and the mean diameter and cross sectional area of the cholinergic cell bodies were similar. The cholinergic hippocampal innervation, as measured by the density of acetylcholinesterase-positive fibers in the outer molecular layer of the dentate gyrus was also similar across all ages. These parameters also did not change during aging in p75(NGFR) -/- mice and the number and size of the choline acetyltransferase-positive neurons and the cholinergic innervation density were largely similar as in control mice at all ages. These results suggest that p75(NGFR) does not play a major role in the maintenance of the number or morphology of the cholinergic basal forebrain neurons during aging of these mice. Alternatively, p75(NGFR) -/- mice may have developed compensatory mechanisms in response to the absence of p75(NGFR).
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PMID:Cholinergic medial septum neurons do not degenerate in aged 129/Sv control or p75(NGFR)-/-mice. 1079 57


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