Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have characterised the distribution of choline acetyltransferase (ChAT) mRNA in spinal cord from normal and motor neurone disease/amyotrophic lateral sclerosis (MND) subjects by in situ hybridisation. High concentrations of ChAT-mRNA were detected in 4 main regions of spinal cord, layer IX of the ventral horn, layer III of the dorsal horn, the intermediate grey matter and layer X around the central canal. ChAT mRNA was most highly concentrated in layers IX and III. Substantial decreases in ChAT mRNA were detected in ventral grey matter (layer IX) of cervical and lumbar cord in all cases of MND. Smaller and more variable changes in ChAT mRNA were seen in MND in other regions of spinal cord which indicates that these changes may arise as secondary processes. The value of this technique in understanding the pathophysiology of MND is discussed.
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PMID:Characterisation of the distribution of choline acetyltransferase messenger RNA in human spinal cord and its depletion in motor neurone disease. 146 22

The cholinergic-specific gangliosides Chol-1 alpha and beta were detected in human brain and spinal cord by immune staining of thin-layer chromatography (TLC) plates on which ganglioside extracts had been separated. The colocalization of choline acetyltransferase (ChAT) and the Chol-1 antigens in ventral horn motoneurons was demonstrated immunocytochemically. In analytical studies, Chol-1 was found to be more concentrated in dorsal cord than ventral but the reverse was true of ChAT. This difference was explained by differences in the subcellular location of the two markers. Within each region of the thoracic cord the levels of ChAT and Chol-1 in different cords showed covariance. The expected fall of ChAT and Chol-1 in amyotrophic lateral sclerosis (ALS) cords was not seen and possible reasons for this are discussed.
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PMID:Chol-1 is a cholinergic marker in the human central nervous system. 151 93

We analyzed binding sites for quinuclidinyl benzilate (QNB) and hemicholinium-3 (HC-3) by quantitative slice autoradiography and the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in spinal cord of 5-7 patients with amyotrophic lateral sclerosis (ALS). In the ventral horn, QNB binding sites were markedly reduced (38% of controls; P less than 0.001), whereas HC-3 binding sites were only moderately affected (76%, P less than 0.01). Losses in cholinergic marker enzymes were inconsistent. The loss of muscarinic binding sites in the ventral horn was the most reliable cholinergic disease marker in ALS.
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PMID:Cholinergic markers in ALS spinal cord. 162 47

Embryonic human spinal cord cells have been grown in dissociated monolayer cultures for 1 to 7 weeks. Using cell type specific markers, it was possible to show that the cultures contain neurons, astrocytes and fibroblasts. Electrical membrane properties were studied with patch electrodes using the whole cell recording technique. Neurons had short duration action potentials that could be blocked by tetrodotoxin. The membrane currents in these neurons were studied in voltage clamp experiments. Three types of voltage-dependent currents were observed: a sodium current; a potassium current made up of two components, IA and IK; and a calcium current. Both cholinergic and GABAergic neurons are present in the cultures. There is more choline acetyltransferase activity in cultures prepared from the anterior as compared to the posterior part of the spinal cord, suggesting that the cultures contain motoneurons. This tissue culture preparation was developed for the study of amyotrophic lateral sclerosis; we have been unable to detect the presence of any toxic agent from the serum of these patients on the cultured cells. Experiments are in progress to purify the motoneurons using Percoll gradients.
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PMID:Characterization of dissociated monolayer cultures of human spinal cord. 271 16

Activities of choline acetyltransferase (ChAT) were microassayed in individual cell bodies of motor neurons, isolated from freeze-dried sections after autopsy of lumbar spinal cords from four patients with sporadic amyotrophic lateral sclerosis (ALS) and four control patients with nonneurological diseases. Numerous large neurons were found in the anterior horn at the early degeneration stage of ALS, but the cell bodies atrophied and decreased in number at the late advanced stage. The small, atrophied neurons were very fragile and were easily destroyed during the isolation procedure with a microknife. The average activity, expressed on a dry weight basis, of 58 ALS neurons was lower than that of 67 control neurons. The large, well-preserved neurons at the early nonadvanced stage had markedly lower ChAT activities than control neurons. The specific activity gradually increased with the progress of atrophy but did not return to the control level.
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PMID:Choline acetyltransferase activities in single spinal motor neurons from patients with amyotrophic lateral sclerosis. 291 Oct 33

The purpose of this paper is to illustrate the advantages of the chemo-morphological approach in the study of pathological material. On one hand, the analysis of selected pathological cases (amputations, spinal transections) is able to provide invaluable information concerning the cells of origin of certain spinal transmitters in the human being. On the other hand, chemical neuropathology allows a more precise identification of the neuronal nets or types that are involved in a disease process. This advantage is underlined by studies performed in amyotrophic lateral sclerosis. In this condition, certain modifications, such as the reductions of acetylcholinesterase, choline acetyltransferase, cholinergic muscarinic, glycine or TRH receptors, are probably a consequence of motoneuron degeneration. In contradistinction, other findings, such as specific metabolic changes of motoneurons or early disappearance of SP-containing fibers in lamina IX, might be relevant for the pathogenesis of the disease.
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PMID:[Amyotrophic lateral sclerosis. Physiopathology and experimental models. Chemical neuroanatomy of the human spinal cord: applications to pathologic cases including amyotrophic lateral sclerosis]. 306 77

A preparation of dissociated monolayer cultures from embryonic human spinal cord has been developed and characterized (Kato, Touzeau, Bertrand, Bader, 1985) as a model system for the study of amyotrophic lateral sclerosis (Touzeau and Kato, 1986). The cultures contain cholinergic and GABAergic neurons, astrocytes and fibroblasts. We have recently found that gamma-interferon (IFN) can increase the choline acetyltransferase (CAT) activity without altering the level of glutamic acid decarboxylase (GAD) or the neuronal survival; an antibody to IFN can prevent these effects. Gamma-IFN appears to mediate these effects via the non-neuronal cells since in the absence of non-neuronal cells, gamma-IFN has no effect on the cholinergic properties. The non-neuronal cells alone have no CAT or GAD activity. Astrocytes may be responsible for these changes since gamma-IFN increases the development of GFAP immunoreactivity in cultures of 6-7 week old spinal cord cells and it causes no visible change in the Thy-1 immunoreactivity of the fibroblasts. Thus we propose that IFN acts on non-neuronal cells, possibly the astrocytes, which in turn stimulate neuronal cholinergic traits either by means of a diffusible factor or via cell-cell contact. These studies could be relevant in understanding the effects of the immune system on the nervous system and also in the search for new drugs which act specifically on cholinergic neurons.
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PMID:[Interferon stimulates the expression of cholinergic properties in human spinal cord neurons in culture]. 314 83

The hypothesis that amyotrophic lateral sclerosis (ALS) might be the disorder of "motor nerve growth factor" has been proposed, being based on the results of the research in tissue culture. The evidence of putative growth factor for spinal motor neurons has been searched, but not found yet. To investigate the growth factor for cultured rat fetal ventral spinal cord neurons two experiments were carried out. One experiment was to evaluate the rat fetal age-related dependency or requirement of putative growth factor in fetal calf serum and non-neuronal cells in cultured ret fetal ventral spinal cord neurons. Another experiment was the evaluation of the possibility as the growth factor of insulin, 5-alpha dihydrotestosterone, epidermal growth factor and fibroblast growth factor for cultured rat fetal ventral spinal cord neurons. The following results were obtained from these experiments; Insulin was found to be acting like a growth factor for rat fetal ventral spinal cord neurons, showing neurite promoting effect and choline acetyltransferase activity stimulating effect. 5-alpha dihydrotestosterone had neurite promoting effect on cultured rat fetal ventral spinal cord neurons without choline acetyltransferase activity stimulating effect. Epidermal growth factor and fibroblast growth factor which are regarded as insulin-related growth factor did not show apparent neurotrophic effect on cultured rat fetal ventral spinal cord neurons. There was a big difference in dependency or requirement of putative growth factor in fetal calf serum and non-neuronal cell between cultured rat fetal 13-15 day old ventral spinal cord neurons and cultured rat fetal 16-18 day old fetal ventral spinal cord neurons. It is necessary to consider about the rat fetal age on the evaluation of the effect of putative growth factor for cultured rat fetal ventral spinal cord neurons.
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PMID:[Investigation of a growth factor for cultured rat fetal spinal motor neurons]. 352 86

Dissociated human spinal cord cells were grown in monolayer cultures in the presence of serum from normal controls or from patients with ALS or other neurologic diseases. After 20 to 24 days, the levels of choline acetyltransferase, glutamic acid decarboxylase, and lactate dehydrogenase activities were determined in the cultures. On the basis of these biochemical measurements, there was no detectable difference between the effects of the three types of serum on the cultures.
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PMID:ALS serum has no effect on three enzymatic activities in cultured human spinal cord neurons. 396 Mar 35

In three patients dementia without neurofibrillary tangles or Pick bodies antedated amyotrophy by several years. The motor neuron disorder in two patients was characterized by terminal bulbar symptoms; in one it was similar to classic amyotrophic lateral sclerosis. In two patients, quantitative studies of selected regions of the cortex using a computerized image analyzer disclosed, as in patients with senile dementia of Alzheimer type, a marked reduction in the number of neurons, especially those larger than 90 mu 2. The findings differed from those in Alzheimer dementia, however, in that the cells in the substantia innominata were not reduced and the levels of choline acetyltransferase and somatostatin-like immunoreactivity, determined in one patient, were within normal limits. A variable degree of sponginess of the upper layers of the cortex was attributed to attrition of pyramidal cell dendrites, observed in the one patient in whom Golgi study was successful. Because of severe degeneration of the substantia nigra in all three, the disease in these patients may represent a subset of motor neuron disease or a multisystem atrophy.
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PMID:Dementia and motor neuron disease: morphometric, biochemical, and Golgi studies. 614 12


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