Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) among the Chamorros in Guam is remarkably high. The patients with ALS have clinical and pathological characteristics similar to those in other parts of the world. The PDC patients display parkinsonism and progressive dementia and show a characteristic neuronal loss in certain parts of the central nervous system such as the hippocampus and substantia nigra. The Guamanian patients with ALS and PDC commonly have widespread Alzheimer's neurofibrillary changes, but without the associated senile plaques. We have applied immunohistochemical procedures to examine the expression of marker substances in Guamanian ALS and PDC. The markers studied include tau protein, ubiquitin, beta proteins, synaptophysin, calcineurin, Met-enkephalin, substance P and tyrosine hydroxylase. The results were compared with the findings in patients with Alzheimer's disease, Parkinson's disease, sporadic ALS and familial ALS.
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PMID:Amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam: immunohistochemical studies. 158 17

The numbers of silver-stained senile plaques and plaques containing tyrosine hydroxylase (TH)-like immunoreactivity were counted in the neocortex, amygdala and hippocampus of control subjects and patients with Alzheimer's disease, and compared with the density of TH-positive nerve fibers. The number of silver-stained senile plaques was lowest in the hippocampus and highest in the amygdala, and increased in all three structures in relation to the degree of dementia in the patients. A small proportion of plaques in the hippocampus of the most demented subjects and a large proportion of plaques in the amygdala were TH-positive. No TH-like immunoreactivity was found in plaques in the neocortex, although this structure contained almost as many silver-stained senile plaques and was as densely innervated by TH-positive fibers as the amygdala. The number of plaques containing TH-like immunoreactivity was, therefore, not proportional to the innervation of the structures by TH-positive fibers, nor to the total number of plaques in the structure, suggesting that the dissociation between the proportion of TH-positive plaques in the amygdala and neocortex may be due to differences in the populations of TH-positive fibers innervating the structures.
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PMID:Tyrosine hydroxylase-like immunoreactivity in senile plaques is not related to the density of tyrosine hydroxylase-positive fibers in patients with Alzheimer's disease. 197 Jan 42

In the present study we investigated the effects of the anti-dementia drug calcium D-(+)-4-(2,4-dihydroxy-3,3-dimethyl-butyramido) butyrate hemihydrate (hopantenate) on the dopaminergic neurons of rats, and also compared the effects of the drug on dopaminergic neurons in young adult rats (4 months old) and aged rats (21 months old). Hopantenate 1000 mg/kg, p.o. significantly increased striatal dopamine (DA) levels, but displayed almost no effect upon the DOPAC and HVA levels. Furthermore, we investigated the effects of hopantenate upon tyrosine hydroxylase activity by examining NSD-1015-induced L-DOPA accumulation and found that hopantenate 1000 mg/kg, p.o. significantly increased the L-DOPA accumulation. In addition, comparing the effect of hopantenate on dopaminergic neurons in young adult rats and aged rats, we found that the striatal DA, DOPAC and HVA levels were decreased as a concomitant of aging, and hopantenate 1000 mg/kg, p.o. significantly increased DA and DOPAC levels in both ages. The above results clearly indicate that hopantenate enhanced DA biosynthesis by stimulating the activity of tyrosine hydroxylase. Furthermore, the results of hopantenate upon dopaminergic neurons in young adult rats and aged rats suggest that sensitivity to the drug may not be different with age, though the striatal DA, DOPAC and HVA levels of rats were decreased as a concomitant of aging.
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PMID:Effects of the anti-dementia drug hopantenate calcium upon striatal dopaminergic neurons in young and aged rats. 257 May 56

A quantitative study of the morphology and distribution of norepinephrinergic neurons in the human locus coeruleus (LC) is given for normal young and older adult brain. Norepinephrine (NE)-producing neurons are identified by immunocytochemistry of two NE biosynthetic enzymes, tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), visualized by the peroxidase-antiperoxidase and immunogold-silver-staining methods. TH and DBH immunoreactions yield equivalent results. Both immunocytochemical visualization methods allow detailed analysis of neuronal morphology. The neurons of the human LC fall into four classes: large multipolar neurons with round or multiangular somata, large elliptical "bipolar" neurons, small multipolar neurons, and small ovoid "bipolar" neurons. Though most of the neurons contain neuromelanin pigment, some larger neurons lack pigmentation. Dendritic arborization of all neurons is extensive. Computer-assisted quantitative measurements of the parameters somatic size, dendritic arbor length, surface area, and volume are given. Somatic areas of LC neurons of all four classes are decreased in older adult brain, but dendritic arborization is equally extensive as in the younger. The rostrocaudal length of the LC is approximately 15 mm, and no age-dependent decrease is observed. Computer-assisted mapping of immunoreactive neurons and three-dimensional reconstruction allow division of the LC into rostral, middle, and caudal parts with characteristic distribution of neurons. Small neurons predominate in all parts, but the relative contribution of larger cells decreases in a rostrocaudal direction. A cell loss of 27-37% occurs in older adult brains and to 55% in the brain of a chronically depressed patient without dementia. Cell loss is highest in the rostral part, lower in the middle, and absent in the caudal part, and more small cells are lost than larger ones.
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PMID:Quantitation of catecholamine neurons in the locus coeruleus in human brains of normal young and older adults and in depression. 257 Jul 93

The present study provides qualitative and quantitative investigations of the norepinephrine (NE) neurons in the locus coeruleus (LC) in two neurodegenerative disorders, the senile dementia of the Alzheimer type (SDAT) and Parkinson's disease (PD). The group of PD subjects was subdivided into cases without dementia (P - D), cases with dementia, L-dopa responsive (P + D), and cases with fulminant dementia whose motor disorder symptoms were L-dopa nonresponsive (P + D/L-dopa non-responsive). NE neurons were demonstrated by immunocytochemistry against tyrosine hydroxylase (TH). Quantitations of neuronal parameters and cell numbers and three-dimensional reconstructions of the LC were carried out with a computer-assisted system. In SDAT cases, the rostrocaudal LC length (13 +/- 2.2 mm) is shorter than in controls (14.9 +/- 1.4 mm). The four basic LC neuron classes found in the normal human brain (large multipolar, large "bipolar," small multipolar, and small "bipolar" neurons; Chan-Palay and Asan: J. Comp. Neurol. this issue) are recognizable, but many cell somata are swollen and misshapen with fore-shortened, thick, and less branched dendrites. LC neuron numbers are reduced (between -3.5% and -87.5%). Neuron loss is greatest in the rostral part, less in the middle, and least in the caudal part. In PD cases, the rostrocaudal length (12.4 +/- 1.5 mm) is shorter than in SDAT and controls. The neuronal morphology is more severely altered than in SDAT. The basic neuron classes are hardly distinguishable. Most cell bodies are swollen; they frequently contain Lewy bodies; and the dendrites are short and thin with absent or reduced arborizations. Neuron numbers are more reduced than in SDAT (between -26.4% and -94.4%). Alterations are as severe caudally as rostrally in P - D, and P + D/L-dopa nonresponsive cases. P + D cases are more severely affected rostrally. The presence of depression in SDAT and Parkinson's patients is accompanied by the greatest loss of LC neurons. On the basis of morphological alterations of the TH-immunoreactive neurons, and the degree and topographical distribution of neuron loss, a differentiation is possible between the LC in normal brain and that in SDAT and PD for diagnostic purposes.
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PMID:Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson's disease with and without dementia and depression. 257 Jul 94

Immunohistochemistry with antisera against tyrosine hydroxylase was performed on neurons with Alzheimer's neurofibrillary changes in the substantia nigra and locus ceruleus. These specimens were obtained from brains with Alzheimer's disease, Pick's disease, progressive supranuclear palsy, Alzheimer's type parkinsonism, parkinsonism-dementia complex on Guam, and normal aging. Under these neurologic conditions the affected catecholamine neurons with Alzheimer's neurofibrillary changes were stained positively with antisera against tyrosine hydroxylase. The results suggested that in these neurons, Alzheimer's neurofibrillary changes seemed to develop independently before the reduction of tyrosine hydroxylase protein synthesis.
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PMID:Catecholamine neurons with Alzheimer's neurofibrillary changes and alteration of tyrosine hydroxylase. Immunohistochemical investigation of tyrosine hydroxylase. 285 29

Ten autopsy cases of Progressive Supranuclear Palsy (PSP) are reported. Age at onset ranged from 16 to 67 years and the duration of illness 3 to 24 years. The clinical features were aggressive mental retardation in 4 cases with early onset, paroxysmal dysequilibrium, ophthalmoplegia, rigidity and akinesia, pseudobulbar palsy and variable degrees of dementia. Neuropathology showed widespread neurofibrillary degeneration associated with system-bound neuronal loss and gliosis in subcortical areas, particularly affecting the subthalamic nucleus, substantia nigra, brainstem tegmentum and dentate nuclei, with no or little involvement of the cerebral cortex. The distribution of the lesions and the ultrastructure of the neurofibrillary tangles made of 15 nm straight filaments (seen in one case) in PSP are different from postencephalitic parkinsonism, Guam Parkinson-dementia complex and brainstem affection in (pre)senile dementia. Post-mortem biochemical analysis of two brains disclosed severe reduction of tyrosine hydroxylase, the key synthetic enzyme of the catecholamine pathway, not only in the nigrostriatal system as seen in Parkinson's disease, but in most areas of the brain-stem and limbic system. The implication and possible pathogenic and therapeutic significance of these biochemical findings are discussed. The etiology of PSP and its nosological position within the degenerative extrapyramidal disorders remain unknown.
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PMID:Progressive supranuclear palsy: clinico-pathological and biochemical studies. 610 28

An autopsy case with clinical features of progressive parkinsonism and dementia of presenile occurrence was characterized by the following neuropathological findings: (1) severe degeneration in the striatonigral system and (2) widespread occurrence of numerous senile plaques and Alzheimer's neurofibrillary tangles in the cerebral cortex. We believe this is to be a very rare case of striatonigral degeneration combined with Alzheimer's disease, because, as far as we know, only two similar cases have been reported and they had not such typical characteristics of Alzheimer's disease as ours did. In addition, in our case the biochemical examination revealed that the activity of one of the dopamine-synthesizing enzymes, tyrosine hydroxylase, was greatly decreased in the nigro-striato-pallidal system.
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PMID:Striatonigral degeneration combined with Alzheimer's disease. 611 11

Chronic manganese poisoning is characterized by mental and extrapyramidal disturbances. Parkinsonism-dementia complex (PD) on Guam is also manifested by progressive extrapyramidal syndrome and dementia. In PD, the reduced activities of catecholamine synthesizing enzymes in the brain has been demonstrated. On the other hand, the soil and water in Guam are rich in manganese, and one of the possible etiologic factors is trace element dysmetabolism in PD. The purpose of this paper is to clarify the effect of chronic manganese loading on the central nervous system. Manganese chloride (10 mg/ml of demineralized and distilled water) was administrated orally to Wistar female rats weighing 80-110 g. Six and 12 months after the administration, manganese loaded and control rats were sacrificed by perfusion for histological studies and by decapitation for the assay of tyrosine hydroxylase (TH) activity. The striatum, globus pallidus and substantia nigra were examined with electron microscopy. The brain for TH assay was dissected into four parts as the striatum, midbrain-thalamus, pons-medulla oblongata, and hypothalamus. Ultrastructural changes were overwhelmingly detected in the zona reticulata of the substantia nigra at 12 months. These changes were mainly composed of alterations of the postsynapse and neuronal soma--shrunken and electron dense dendrites accumulated degenerating materials and so-called simple atrophy of the neuron. Alterations in the presynapse were extremely milder than those in the postsynapse and neuron. At both 6 and 12 months, no significant changes in the striatum and globus pallidus were detected except for irregular windings of the plasma membrane in the axon terminal of the globus pallidus at 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Histopathological alteration of the central nervous system in rats, following long-term administration of manganese chloride--relation to the activity of the brain tyrosine hydroxylase]. 614 19

The substantia nigra was examined immunohistochemically using the antibody to tyrosine hydroxylase in 15 patients with sporadic amyotrophic lateral sclerosis (ALS). The number of dopaminergic neurons was diminished in the substantia nigra of seven cases. The diminution was not related to the age, duration of the illness or use of respirators. Supranuclear ophthalmoplegia developed in four and dementia in three out of seven patients with reduction of nigral dopaminergic neurons. In addition, five out of the seven patients developed respiratory failure within 2 years after the onset of the illness. The nigral dopaminergic system may be involved in rapidly progressive ALS patients with supranuclear ophthalmoplegia and/or dementia.
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PMID:Diminution of dopaminergic neurons in the substantia nigra of sporadic amyotrophic lateral sclerosis. 790 81


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