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  • 1
    ISSN: 1435-1463
    Keywords: Tyrosine hydroxylase ; aromatic L-amino acid decarboxylase ; Parkinson's disease ; schizophrenia ; RT-PCR ; mRNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using the reverse transcription-polymerase chain reaction (RT-PCR), we developed a sensitive and quantitative method to detect all four types of human tyrosine hydroxylase (TH) mRNAs in the human brain (substantia nigra). All four types of TH mRNAs were found in the substantia nigra in the control brains examined, and the ratio of type-1, type-2, type-3, and type-4 mRNAs to the total amount of TH was 45, 52, 1.4, and 2.1%, respectively. The average amount of total TH mRNA in the normal brain (substantia nigra) was 5.5 amol of TH mRNA per μg of total RNA. The ratios of four TH isoforms were not altered significantly in Parkinson's disease or schizophrenia. Further we measured the relative amount of aromatic L-amino acid decarboxylase (AADC) and β-actin mRNAs in the brain samples. TH and AADC mRNAs were highly correlated in the control cases. We found that parkinsonian brains had very low levels of all four TH isoforms and AADC mRNAs in the substantia nigra compared with control brains, while no significant differences were found between schizophrenic brains and normal ones. Since the decrease in AADC mRNA was comparable to that in TH mRNA, the alteration of TH in Parkinson's disease would not be a primary event, but it would reflect the degeneration of dopaminergic neurons in the substantia nigra. This is the first reported measurement of mRNA contents of TH isoforms and AADC in Parkinson's disease and schizophrenia.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1463
    Keywords: Fetal brain ; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; 1-methyl-4-phenylpyridinium ion ; catecholamine ; indoleamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of a dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the amounts of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were examined in the whole brains of fetal mice and maternal mice after its administration to pregnant mice. DA and DOPAC concentrations were decreased significantly in both the fetal and maternal brains. At 3 hr after injection, reduction of the DOPAC concentration was more marked than that of DA in both the fetal and maternal brains. Increase of 5-HT concentration was observed until 12 hr after injection in the fetal brains and 6 hr in the maternal brains. These results indicate that 1-methyl-4-phenyl-pyridinium ion (MPP+) and MPTP affect the levels of catechol- and indoleamines in the brain of premature stage as well as in the mature brain.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-4919
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary 1. Oudenone, an inhibitor of tyrosine hydroxylase, and fasaric acid, an inhibitor of dopamine-β-hydroxylase, both newly described inhibitors of microbial origin showed more pronounced hypotensive effects on spontaneously hypertensive rats than on normotensive Wistar rats. 2. Spontaneously hypertensive rats had about 2-fold highe tyrosine hydroxylase and dopamine-β-hydroxylase activities in adrenal glands, and lower tyrosine hydroxylase activity in mesenteric artery. After adrenalectomy, blood pressure of spontaneously hypertensive rats decreased, and the lower tyrosine hydroxylase activity in mesenteric artery increased to the enzyme level of normotensive Wistar rats.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Neurochemical research 15 (1990), S. 425-429 
    ISSN: 1573-6903
    Keywords: Tyrosine hydroxylase ; Parkinsonian brain ; MPTP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Changes in homospecific activity (unit of enzyme activity per unit of enzyme protein; Rush, Kindler and Udenfriend, 1974. Biochem. Biophys. Res. Commun., 61, 38) of tyrosine hydroxylase (TH) in the striatum of the brain were examined in MPTP-treated mice and parkinsonian patients. After a single injection of MPTP to mice, TH activity was acutely inhibited onlyin situ without changes in in vitro TH activity (Vmax) and TH protein; TH homospecific activity (TH Vmax/TH protein) did not change. After repeated injection of MPTP to mice for 8 days, in situ TH activity, in vitro TH Vmax, and TH protein were decreased in parallel, and TH homospecific activity did not change The result indicates that the decreases in in situ TH activity and in TH Vmax are due to the decrease in TH protein by nerve degeneration of dopaminergic neurons in MPTP treated mice. However, when MPP+ was infused in the striatum of rats for 3 hours, in vitro TH activity (Vmax) was decreased without changes in TH protein. Thus, TH homospecific activity was decreased. The results indicate that MPP+ inactivates TH protein in the striatum after continued infusion. In contrast, the homospecific activity of TH in post-mortem parkinsonian striatum was increased 3-fold. The increase in homospecific activity of residual TH in parkinsonian brain suggests such molecular changes in TH molecules as result in a compensatory increase in TH activity.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1435-1463
    Keywords: Transgenic mice ; tyrosine hydroxylase promoter ; chloramphenicol acetyltransferase ; aromatic L-amino acid decarboxylase ; ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have produced transgenic (Tg) mice carrying 5.0-kb fragment from the 5′-flanking region of the human tyrosine hydroxylase (hTH) gene fused to a reporter gene, chloramphenicol acetyltransferase (CAT) [Sasaoka et al. (1992) Mol Brain Res 16: 274–286]. In the brain of the Tg mice, CAT expression has been observed in catecholaminergic (CAnergic) neurons and also in non-CAnergic neurons. The aim of the present study is to examine in detail the cell-type specific expression of the hTH-CAT fusion gene in the brain of the Tg mice, by use of immunohistochemistry for CAT, TH, and aromatic L-amino acid decarboxylase (AADC). CAT-immunoreactive cells were found in CAnergic brain regions which contained TH-positive cells, and also in non-CAnergic brain regions which contained no TH-labeled cells. The non-CAnergic brain regions that represented CAT-stained cells were further divided into two groups: (i) regions containing AADC-labeled cells, for example, bed nucleus of the stria terminalis, nucleus suprachiasmaticus, mammillary body, nucleus raphe dorsalis, inferior colliculus, and nucleus parabrachialis, and (ii) regions containing no AADC-positive cells, for example, main olfactory bulb (except A16), accessory olfactory bulb, nucleus olfactorius anterior, caudoputamen, septum, nucleus accumbens, hippocampus, medial nucleus of the amygdala, entorhinal cortex, nucleus supraopticus, and parasubiculum. The results indicate that the 5.0-kb DNA fragment flanking the 5′ end of the hTH gene may contain the element(s) specific for neuron-specific TH expression but which may be insufficient to attenuate ectopic expression.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1435-1463
    Keywords: Tyrosine hydroxylase ; tryptophan hydroxylase ; biopterin ; anorexia nervosa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activities of tyrosine hydroxylase and tryptophan hydroxylase and contents of biopterin and neopterin were measured for the first time in various regions of human brain from a patient with anorexia nervosa (AN). In AN as compared with controls, tyrosine hydroxylase activity was markedly reduced in all brain regions analyzed, while tryptophan hydroxylase activity and biopterin content had a tendency to increase. Neopterin content did not change dramatically. The opposite changes of tyrosine hydroxylase and tryptophan hydroxylase suggest an imbalance between the activity of catecholaminergic neurons and that of serotonergic neurons, and may be related to pathogenesis of AN.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1435-1463
    Keywords: Dopamine β-hydroxylase ; cerebrospinal fluid ; development ; epileptic children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The developmental change of dopamine β-hydroxylase (DBH) activity in cerebrospinal fluid (CSF) of epileptic children was studied. Non-epileptic children showed lower DBH activity in CSF than adult, and its activity increased with age. In contrast, epileptic children showed no increase in DBH activity with age. DBH in CSF may be a good index of noradrenergic function in child brain. The results on developmental change in DBH in CSF suggest that refractory epilepsy with long term medication has decreased activity in central noradrenergic neurons.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1435-1463
    Keywords: Dopamine ; dopaminergic neuron ; locomotor activity ; methamphetamine ; nicotine ; transgenic mice ; tyrosine hydroxylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We produced transgenic (Tg) mice carrying the human tyrosine hydroxylase (TH) gene. To investigate differences in the dopaminergic (DAergic) neuronal activity between the Tg and nTg mice, we examined changes in the locomotor activity induced by methamphetamine (MAP) and nicotine (NIC), which enhances DA release and induces TH enzyme activation, respectively. Surprisingly, however, the intensity of MAP (2.5 mg/kg, once a day for 14 days)-induced hyperlocomotion in the nTg mice was greater than that in the Tg mice, and, furthermore, the Tg mice were less sensitive to subacute administration of NIC (0.5 mg/kg, once a day for 14 days) than the nTg mice. These results suggest that DAergic neuronal function is suppressed in Tg mice to compensate for the overexpression of TH.
    Type of Medium: Electronic Resource
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