Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 studied 4 siblings (3 men and 1 woman), ages 22 to 43 years, with congenital ptosis, external ophthalmoplegia, proximal muscle weakness and fatigability unresponsive to acetylcholinesterase (AChE) inhibitors. Repetitive nerve stimulation showed a significant compound muscle action potential (CMAP) area decrement at 2 or 3 Hz. Nerve conduction studies and concentric needle electromyography were normal, and repetitive CMAPs to single nerve stimulation were not observed. Voluntary single fiber electromyography (SFEMG) showed increased jitter and blocking. Assessment of individual end-plates using SFEMG with intramuscular axonal microstimulation showed no uniform relationship between jitter and the rate of stimulation, consistent with a postsynaptic defect of neuromuscular transmission. Edrophonium eliminated the decremental response to repetitive nerve stimulation, but caused no significant clinical improvement, suggesting an additional mechanism for weakness in these patients.
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PMID:A congenital myasthenic syndrome refractory to acetylcholinesterase inhibitors. 131 43

The acetylcholinesterase activity (AChE) in the human subfornical organ (SFO) was detected by the method of Koelle and Friedenwald in 16 human brains collected between 6 and 12 hrs postmortem. The only AchE-positive structures found were neuronal cell bodies and processes, morphologically classified as stellate and fusiform neurons of large, medium and small size. Large ones prevailed in the dorsal zone. The neurons were homogeneously distributed in the rostral area of the SFO. The penetration and ramification of large blood vessels produced a decreasing neuronal density in the medium-caudal area. The architecture of the SFO in sagittal sections comprised a central zone with neurons juxtaposed to the walls of the vascular plexus, whose dendritic and axonal processes showed an intricate pattern without a special arrangement. This neuronal zone of the SFO was surrounded by a peripheral layer of neurons with axonal projections to the rostral area. This layer was thicker in the dorsal zone of the SFO, where axonal fibers "climbing-up" from the central perivascular neurons could be demonstrated. In coronal sections some neurons with prolongations of arcuate distribution connected the dorsal and ventral zones.
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PMID:Acetylcholinesterase activity in the human subfornical organ. 136 51

Previous studies have demonstrated that cholinergic neurons in the adult rat forebrain, i.e., septal region, are able to respond and regenerate after damage followed by exogenous treatment with beta-nerve growth factor. Furthermore, it has been shown that an age-related loss of NGF-receptor (NGFr) immunoreactivity occurs in cholinergic septal neurons. Since the regenerative capacity of cholinergic neurons is of importance for potential therapeutic strategies during the course of age-related neurodegenerative diseases, we have compared NGFr positive neurons in young adult (3 months old) and in aging (18-24 months old) rats in their ability to produce a physiological plasticity response after surviving an excitotoxic lesion of the nucleus basalis of Meynert (NBM). In aging control rats, NGFr immunoreactivity within NBM neurons was significantly reduced, in analogy to data obtained earlier from studies about septal neurons in aged rats. After lesion with quisqualic acid, a severe cell loss as well as atrophy of remaining cholinergic neurons was observed in both groups. Investigation of the NBM at various times after the lesion demonstrated signs of axonal or dendritic sprouting and local regeneration, with a maximum seen 3 months after the lesion. No age-related differences in the response could be found. However, despite local fiber growth, no reinnervation of the frontal and parietal cortex could be noted, as demonstrated by acetylcholinesterase histochemistry. Our findings suggest that, despite a relatively early onset of NGFr decline during lifetime, cholinergic cells keep the capacity for a plastic response, although they ultimately fail to reinnervate the neocortex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quisqualic acid-induced lesion of the nucleus basalis of Meynert in young and aging rats: plasticity of surviving NGF receptor-positive cholinergic neurons. 139 63

Using the monoclonal antibody, ME 20.4, against the p75 nerve growth factor (NGF) receptor, NGF receptor-like immunoreactivity has been identified in axonal processes innervating the human hippocampus, where previously a loss of reactivity has been reported in a preliminary study of Alzheimer's disease [10]. In an extended analysis of 15 cases of Alzheimer's disease, the number of NGF receptor positive fibres in the fimbria and alveus was generally decreased compared with age-matched normal groups, in presenile but not senile cases (differentiated by age of onset before or after 65 years). By contrast, in 5 demented Parkinson's disease cases (aged 61-86 years at death) immunohistochemically reactive fibres were consistently minimal or absent. This pattern of NGF receptor loss in the hippocampus most closely reflects the loss of basal forebrain cholinergic neurones, previously reported within the different clinical groups but not by biochemical measures of cholinergic function. It is concluded that even at moderately advanced stages of Alzheimer's disease with onset in the senium, axonal processes and NGF receptor mechanisms may be structurally intact in areas of cholinergic innervation from the basal forebrain, despite evidence of cholinergic dysfunction (decreased choline acetyltransferase (ChAT) and acetylcholinesterase), but that in presenile Alzheimer's and in demented Parkinson's disease cases the receptor declines in conjunction with the loss of subcortical neurones and their processes. The loss of ChAT activity may therefore reflect a dysfunction of the NGF system, in its normal maintenance of the cholinergic phenotype in basal forebrain neurones.
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PMID:Hippocampal nerve growth factor receptor immunoreactivity in patients with Alzheimer's and Parkinson's disease. 143 50

Fetal rat neocortex grafted into lesion cavities made in the newborn rat neocortex can exchange multiple axonal connections with the host brain. Most previous studies demonstrating efferent transplant-to-host brain connections have used fluorescent retrograde tracers injected into the host brain (Castro et al. 1985, 1987; Floeter and Jones 1984; O'Leary and Stanfield 1989). Other studies have used anterograde axonal tracing with either tritium-labelled amino acids impregnating the transplant and its efferents (Floeter and Jones 1985) or horseradish peroxidase injected into the transplants (Chang et al. 1984, 1986). In the present study we used the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) to examine in detail the course and termination of the efferent neocortical graft fibers. Twenty-six newborn rats had the right frontal cortex forepaw area removed by vacuum aspiration, while anesthetized by hypothermia. A piece of fetal frontal cortex 14-16 embryonic days old (E14-16) was immediately thereafter placed in the lesion, and the recipient rats allowed to survive for 5-7 months. At this time the rats were reoperated under sodium pentobarbital (Nembutal) anesthesia and the transplants iontophoretically injected with PHA-L. Two weeks later the animals were again anesthetized, perfused, and processed for PHA-L immunocytochemistry and routine histology. Analysis of acetylcholinesterase- (AChE) and Nissl-stained sections showed graft survival in 19 of the 26 animals used in this study. When these 19 brains were processed for PHA-L immunocytochemistry, 5 of them were found with certainty to have the PHA-L injection confined to the transplant. Based on these cases PHA-L-reactive fibers arising from labelled transplant neurons were traced into the ipsilateral host neocortex adjacent to the transplant and found to project through the subcortical white matter to the ipsilateral parietal neocortical area 1, and claustrum. Callosal fibers were traced to the contralateral frontal neocortical forelimb and parietal areas. Transplant fibers were also observed to descend through the caudate putamen in the dispersed fiber bundles of the internal capsule to distribute as terminal branches and varicose fibers within the mesencephalic periaqueductal gray, red nucleus, deep mesencephalic nucleus, and intermediate gray of the superior colliculus, as well as in the pontine gray. Similar fibers and terminations were present in the caudate putamen, the reticular, ventrobasal, centrolateral, posterior, and parafascicular thalamic nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Projections from fetal neocortical transplants placed in the frontal neocortex of newborn rats. A Phaseolus vulgaris-leucoagglutinin tracing study. 149 66

The introduction of transplants consisting of cultured Schwann cells and their associated extracellular matrix (Sc/ECM) into a central nervous system (CNS) lesion cavity facilitates axonal regeneration from injured, adult mammalian neurons with subsequent reinnervation of their appropriate target (Kromer and Cornbrooks: Proceedings of the National Academy of Sciences of the United States of America 82:6330-6334, 1985). In the present study, the effects of a delayed transplantation procedure on the time course of this regenerative response were evaluated. For these experiments, bilateral CNS lesions were created between the septum and hippocampus by removing the fimbria-fornix pathway. Lesion cavities received either no transplants, transplants of collagen, or Sc/ECM transplants at the time the lesion was created or 6 days later. When no transplants or transplants of collagen were used, axonal sprouts extended for very short distances into the lesion cavity. These axons were not preferentially associated with the collagen transplants nor maintained at long post-lesion survival times. In animals that received Sc/ECM transplants, the number of sprouting axons and the progression of axonal growth along the transplants was much more extensive than for the collagen transplants. Although more axons were detected in cavities that received transplants immediately after the fimbria-fornix lesion, axonal regeneration along the transplants was similar regardless of whether there was a delay in transplanting the Schwann cells. By using histochemical techniques to identify acetylcholinesterase (AChE), regenerating AChE-positive axons were first detected in the cavity at 3 days post-transplantation, were associated with the Sc/ECM transplants by 5 days, and crossed the cavity within 8 days post-transplantation. Regenerating, neurofilament-positive axons crossed the CNS-Sc/ECM transplant interfaces in association with laminin-positive, glial fibrillary acidic protein-positive cellular pathways. Upon reaching the caudal end of the Sc/ECM transplant, the cholinergic axons abandoned the transplant and oriented directly toward the adjacent hippocampus. Both the simultaneous and delayed transplantation paradigms demonstrated a similar reinnervation pattern of AChE-positive fibers in the hippocampus, but there was a more rapid penetration and more extensive arborization of fibers in animals receiving the delayed transplants. Cholinergic fibers initially invaded the dentate gyrus molecular layer and hilus between 8 and 14 days post-transplantation. By 45 days post-transplantation, AChE-positive axons were detected throughout the dentate gyrus and regio inferior, but few fibers were present in regio superior of the hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of delayed transplantation of cultured Schwann cells on axonal regeneration from central nervous system cholinergic neurons. 154 22

In a previous report, we demonstrated in vivo ameliorating effects of conjugated estrogen in women suffering from senile dementia-Alzheimer's type. To investigate the effects of estrogen on the growth of cholinergic neurons, the present study was performed using rat cholinergic tissue implanted into the anterior chamber of the eye. Fetal diagonal band tissue containing cholinergic neurons was grafted into the anterior eye chamber of adult female rats that had either been treated or not with 2 mg estradiol valerate injected every 3 days after oophorectomy. Two and four weeks after transplantation, the axonal and/or dendritic growth of cholinergic neurons in the graft was studied using acetylcholinesterase histochemistry. At both times, acetylcholinesterase positive processes were densely distributed in the grafts of estradiol valerate treated rats, while in rats without estradiol valerate treatment acetylcholinesterase positive reaction was essentially localized only on the cell bodies. These findings were more obvious at 2 weeks after transplantation than at 4 weeks. These results suggest that estrogen acts on cholinergic neurons as a growth factor.
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PMID:Estrogen as a growth factor to central nervous cells. Estrogen treatment promotes development of acetylcholinesterase-positive basal forebrain neurons transplanted in the anterior eye chamber. 156 34

This study is focused on the survival of fetal neocortical grafts placed in the infarcted adult host cortex of the spontaneously hypertensive rat and describes the ability of host axonal regeneration into the graft after a focal ischaemic lesion. Five to seven days following ligation of the right middle cerebral artery, dissociated neocortical primordium from fetuses of gestational age 12-18 days was implanted into the infarcted cortical area. Surviving transplants were seen in all rats, although grafts derived from gestational age 12-14 days displayed an irregular morphology rich in sinusoid-like cavities and containing fewer cells of apparently mature neuronal morphology. Grafts from older donors contained perikarya of neuronal appearance; however, they lacked normal cortical lamination. Ten days postgrafting, fibers stained by acetylcholinesterase histochemistry, dopamine-beta-hydroxylase, and 5-hydroxytryptamine immunohistochemistry were found in the grafts, and by 10-23 weeks after transplantation the fiber density had increased substantially. When the retrograde tracer Fluoro-Gold was injected into the grafted tissue, labeled cells were found in several subcortical nuclei of the host, including the nucleus basalis of Meynert, ventral pallidum, thalamus, dorsal raphe, locus coeruleus, as well as the ipsilateral and contralateral neocortex. This study shows that grafts of dissociated neocortical tissue exhibit good survival and growth potential when implanted into infarcted neocortex and that several nerve fiber systems of the adult host have a regenerative capacity sufficient to innervate the grafted tissue.
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PMID:Fetal neocortical grafts implanted in adult hypertensive rats with cortical infarcts following a middle cerebral artery occlusion: ingrowth of afferent fibers from the host brain. 157 19

Regeneration of central nervous system (CNS) axons has been studied in the cholinergic septo-hippocampal system using various 'bridges' able to support fiber growth. In this study, a pure Schwann cell (Sc) suspension labeled with bisbenzimide (Hoechst 33342) was grafted in the lesioned septo-hippocampal pathway. At 2 weeks post-grafting, acetyl-cholinesterase (AChE)-positive fibers invaded the graft and grew in association with the Hoechst-labeled Sc, some of which expressed the low-affinity nerve growth factor receptor (NGF-R). At 2 months and 4 months post-grafting, the dorsal hippocampus was reinnervated with an apparently normal innervation pattern. Analysis of fiber growth in the hippocampus at four months post-grafting revealed a significant increase of reinnervation in the grafted animals (2 mm) compared to the non-grafted ones. No difference was observed in the number of cholinergic septal neurons expressing the NGF-R. These results demonstrate that a Sc suspension grafted into the lesioned septo-hippocampal system, integrates well into the host tissue, and supports axonal CNS outgrowth, implying that Sc by themselves provide an adequate environment for regeneration to occur.
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PMID:Pure Schwann cell suspension grafts promote regeneration of the lesioned septo-hippocampal cholinergic pathway. 161 12

The organization of the thalamostriatal projections arising from the centromedian (CM) and parafascicular (Pf) thalamic nuclei in the squirrel monkey (Saimiri sciureus) was studied at both light and electron microscopic levels. Following selective injections of the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into the CM or Pf, patterns of terminal arborization within the striatum were compared to the biochemical heterogeneity of the striatum as revealed by immunohistochemical staining for the calcium-binding protein calbindin D-28k (CaBP), and histochemical staining for the enzymes acetylcholinesterase (AChE) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-diaphorase). The PHA-L-labeled axon terminals within the striatum were further analyzed at the ultrastructural level to characterize their pattern of synaptic organization. Dense and heterogeneous terminal fields occur in the "sensorimotor" territory of the striatum after CM injections, or in the "associative" striatal territory following Pf injections. In the associative territory labeled axons arborize in a diffuse manner predominantly within areas enriched with CaBP, AChE, or NADPH-diaphorase, representing the matrix compartment, and tend to avoid areas poor in these substances, corresponding to the patch/striosome compartment. In the sensorimotor territory labeled axons form bands that occupy a subregion of the NADPH-diaphorase-rich zone in the putamen. The terminal pattern of the CM-striatal projection suggests the existence of a more complex mosaic organization within the sensorimotor territory. Ultrastructural analysis of PHA-L-labeled elements within the striatum reveals that both CM and Pf projections form asymmetric synapses upon dendrites and spines of striatal cells. A total of 339 PHA-L-labeled boutons were examined after CM injections and compared to 293 boutons following Pf injections. After CM injections, 29% of PHA-L-labeled terminals form synapses on dendritic spines and 66% on dendritic shafts, whereas after Pf injections only 12% of synapses occur on dendritic spines compared to 81% on dendritic shafts. Labeled terminals forming axosomatic or axoaxonic synapses were not seen within the striatum following either CM or Pf injections. It is concluded that in the squirrel monkey: 1) Pf-striatal fibers profusely arborize within the matrix compartment of the associative territory, 2) CM-striatal fibers form bands that occupy a subregion of the NADPH-diaphorase-rich zone within the sensorimotor territory, and 3) that both Pf- and CM-striatal projections establish asymmetric synapses with dendrites and spines of medium-sized spiny cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a light and electron microscopic study of the thalamostriatal projection in relation to striatal heterogeneity. 161 51


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