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

The effects of neonatal infection, perinatal malnutrition, and crowding on the metabolism of brain catecholamine were studied in specific pathogen-free mice. Metabolic turnover of catecholamine was determined by measuring the incorporation of precursor tyrosine-(14)C into brain tissue, catabolic activity of norepinephrine-(3)H at various times after intracisternal injection, and tissue levels of dopamine and norepinephrine. The rate of tyrosine incorporation was decreased by neonatal infection but was increased by perinatal malnutrition and crowding. There was no difference in catabolic activity of norepinephrine between infected, crowded, and control groups. In the malnourished group, however, the total radioactivity from norepinephrine was significantly higher than in the control group (1/2) and 2 hr after injection. The brain contents of dopamine and norepinephrine were depressed in the malnourished group. There was no significant difference in catecholamine levels between infected, crowded, and control groups. In the malnourished group, treatment of the mothers with growth hormone prevented almost completely weight loss during lactation, and also resulted in higher fetal weight. Hormone treatment restored to normal the levels of brain catecholamine and the enzymatic activity of brain tyrosine hydroxylase in progeny of malnourished mothers.
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PMID:Lasting biological effects of early environmental influences. 8. Effects of neonatal infection, perinatal malnutrition, and crowding on catecholamine metabolism of brain. 508 69

The effect of postnatal undernutrition on the catecholamine and serotonin contents of various parts of the brain of suckling rats was examined. Undernourishment was induced by increasing the litter size to 18 pups from day 1 to 21 after birth. In control pups, the total amounts of norepinephrine and dopamine in the whole brain increased greatly during the suckling period (norepinephrine: 17.7 ng at birth, 154 ng on day 10, and 420 ng on day 21; dopamine: 12.6 ng at birth, 269 ng on day 10, and 1,022 ng on day 21). Similar, but less marked increases in the norepinephrine and dopamine contents of the brain were observed in malnourished pups. The norepinephrine contents of the forebrain, cerebellum, and brain stem of malnourished pups were comparable with those of normal pups on day 10 but the contents of the cerebellum and brain stem were significantly less than those of normal pups on day 21. Postnatal malnutrition also led to a significant decrease in the dopamine content of the forebrain. In contrast, the serotonin content of the brain of undernourished pups was significantly higher than that of controls. The control pups at the end of suckling period were significantly higher than those of undernourished pups (forebrain: 18.3 pmol in controls and 11.5 pmol in malnourished pups; brain stem: 12.3 pmol in controls and 9.8 pmol in malnourished pups). The tyrosine hydroxylase activity (pmol/g) correlated more closely with the norepinephrine content than with the dopamine or norepinephrine plus dopamine content. The tyrosine and phenylalanine contents of the brain were similar in the two groups. It is concluded from these findings that the catecholamine content of the brain is regulated by the enzyme activity rather than the levels of precursor amino acids.
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PMID:Effects of postnatal undernutrition on the catecholamine and serotonin contents of suckling rat brain. 616 Feb 25

Segawa disease (hereditary progressive dystonia with marked diurnal fluctuation) is an autosomal dominant, childhood onset, postural dystonia and the first hereditary basal ganglia disorder whose causative enzyme and gene defect were clarified. The initial symptom is unilateral pes equinovarus with marked diurnal fluctuation. Progression becomes slower after mid-teens and stationary after thirties. Postural tremor may occur after 10 years of age, especially after thirties. Parkinsonian resting tremor action and torsion dystonia. and disturbed locomotion do not occur. L-Dopa shows marked and sustained effect without side effects. F-Dopa PET and [11C] raclopride PET of over 20-year-old cases are normal. Deficiency of GTP cyclohydrolase I (GCH-I) was suggested from low CSF biopterin and neopterin. Mutation of GCH-I gene and decreased GCH-I were clarified as etiology. Twenty-five mutations discordant among families have been found. Autopsy of a gene proven case revealed decreased striatal tyrosine hydroxylase (TH) and dopamine (DA) in ventral striatum where direct pathway is predominant. Decreased GCH-I causes decreased tetrahydrobiopterin (BH4), TH and DA in nigrostriatal (NS) terminal. The lowest affinity of BH4 to TH causes selective involvement of DA. Postural dystonia is caused by decreased TH and DA affecting D1-direct pathway. Thalamic ventrolateral and pedunculo-pontine nuclei are spared. Diurnal fluctuation of symptoms is due to diurnal fluctuation of TH and DA at NS-DA terminal. Decreased DA to below 20% of normal, shown by polysomnographical studies, and its physiological age related decremental changes in NS-DA terminal underlies characteristic clinical course. High D2 receptor before early thirties masks D1 related hypertonus and manifest progression before 20 years of age. Other pteridine abnormalities also cause dopa responsive postural dystonia with diurnal fluctuation. A case of juvenile parkinsonism without dystonia showed decreased TH in dorsolateral putamen where indirect pathway is predominant. These suggest that decreased TH due to decreased BH4 involves D1-direct pathway causing dystonia, and decreased TH itself involves D2-indirect pathway causing parkinsonism.
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PMID:[Segawa disease]. 957 70

Prenatal malnutrition results in increased concentration and release of central noradrenaline, a neurotransmitter that is an important regulator of normal regressive events such as axonal pruning and synaptic elimination. This suggests that some of the functional disturbances in brain induced by prenatal malnutrition could be due at least in part to increased noradrenaline activity that may enhance regressive events during early stages of development. To test this hypothesis we studied whether chronic administration of alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase, to rats during gestation might prevent long-term deleterious effects of prenatal malnutrition on functional properties of interhemispheric connections of the visual cortex, and on asymmetry of visual evoked responses. The experiments were conducted on normal and malnourished rats 45-50 d of age. Prenatal malnutrition was induced by restricting the food consumption of pregnant rats to 40%, from d 8 postconception to parturition. At birth, prenatally malnourished rats had significantly greater whole-brain noradrenaline concentration as well as significantly enhanced noradrenaline release in the visual cortex. At 45-50 d of age, the malnourished group had a significantly smaller cortical area, exhibiting transcallosal evoked responses; in addition, the amplitude of these responses was significantly smaller. Malnourished rats showed a significant reduction of the normal interhemispheric asymmetry of visual evoked responses. The addition of 0.3% alpha-methyl-p-tyrosine to the diet of malnourished pregnant rats during the last 2 wk of gestation prevented functional disorders induced in the offspring by prenatal malnutrition on interhemispheric connectivity of visual areas and on interhemispheric bioelectrical asymmetry, probably by reducing the elevated brain noradrenaline activity and thereby restoring the normal trophic role of this neurotransmitter.
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PMID:Prenatal malnutrition-induced functional alterations in callosal connections and in interhemispheric asymmetry in rats are prevented by reduction of noradrenaline synthesis during gestation. 964 10

Previous reports indicate that malnutrition reduces reproductive functions. We have demonstrated that protein deprivation in the diet also causes reproductive dysfunction by reducing hypothalamic GnRH secretion. Noradrenaline and nitric oxide are modulators of GnRH secretion. Noradrenaline stimulates GnRH secretion and nitric oxide inhibits catecholamine release. This work studies the hypothalamic catecholaminergic and nitrergic neuron activity in Wistar adult male rats fed on an aproteic diet (AP) during 21 days; this treatment was started when rats were 70 days old. Our first experiment studied catecholamine turnover rate after inhibition of tyrosine hydroxylase activity by injecting (i.p.) 400 mg/kg alpha-methyl-p-tyrosine. Our second experiment studied in vitro hypothalamic nitric oxide synthase (NOS) activity in animals under the same diet. AP diet significantly decreased both noradrenaline (P<0.05) and dopamine (P<0.05) hypothalamic turnover rate. Noradrenaline turnover in cerebral cortex was not altered by the aproteic diet. However, hypothalamic NOS activity was not affected in animals fed on an AP diet. These results indicate that the lack of protein in the diet reduces catecholaminergic neuron activity in adult male rats by a NO-independent mechanism, thus suggesting that a decrease in noradrenergic activity may be involved in the reduction of GnRH secretion induced by an AP diet.
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PMID:Aproteic diet decreases hypothalamic catecholamine turnover in adult male rats. 1088 81

To clarify whether a hypo or hyperfunctioning mesocorticolimbic system is the neural substrate of Attention-Deficit Hyperactivity Disorder (ADHD), we carried out a morphometric analysis on an animal model, the Naples high excitability rat (NHE). Male adult NHE and control rats were used for tyrosine hydroxylase (TH) immunocytochemistry in the ventral tegmental area and substantia nigra in coronal cryostat sections. PC-assisted image analysis showed larger DA neurones in the ventral tegmental area but not in the substantia nigra of NHE rats than in controls, associated with a higher expression of TH in the neuropil. Thus, the increased activity and impaired attention of NHE rats are associated with a hyperfunctioning mesocorticolimbic system in this ADHD model.
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PMID:Hypertrophic A10 dopamine neurones in a rat model of attention-deficit hyperactivity disorder (ADHD). 1111 71

The hyperfunctioning dopamine hypothesis in the mesocorticolimbic (MCL) system has been addressed by a neurogenetic approach in model systems. Thus, a morphometric analysis was carried out on neurons of origin of Substantia Nigra (SN) and Ventral Tegmental Area (VTA) dopamine systems of the Naples High-Excitability (NHE), Low-Excitability (NLE) and control lines. Male adult rats were tested in a spatial novelty for indices of activity and non-selective attention. Mesencephalic coronal sections were processed for tyrosine hydroxylase (TH) immunohistochemistry and cytochromoxidase (C.O.) histochemistry. Image analysis in the rostro-caudal plane showed (i) a higher neuron size of TH+ elements in the VTA of NHE and NLE, across the entire structure in the NHE, and only in the middle portion in the NLE; (ii) a higher expression of TH in the neuropil of the VTA in NHE; (iii) a lower C.O. activity in both NLE and NHE; (iv) no differences in the SN. The larger neuron size in both NHE and NLE rats as compared with control rats, along with higher TH expression mainly in the NHE, in absence of any relevant alteration in the SN, reveals an unbalance between the two dopamine systems and a subsequent alteration in limbic (reward, motivation, sustained attention) functions. The decreased C.O. activity might be due to reduced feedback inhibition by striatal GABA neurons and interneurons leading to increased DA neuron firing. In conclusion, the increased behavioral activity and impaired attention observed in the NHE rats are associated to hyperfunctioning MCL system in this genetic model of Attention-Deficit Hyperactivity Disorder (ADHD).
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PMID:A morphometric evidence for a hyperfunctioning mesolimbic system in an animal model of ADHD. 1186 33

L-3,4-dihydroxyphenylalanine, the immediate precursor of dopamine, can be formed by two enzymes: tyrosine hydroxylase (TH) in catecholamine-producing neurons and chromaffin cells and tyrosinase in melanocytes. In this study we examined whether tyrosinase contributes to production of dopamine. Deficiency of TH caused marked reductions in norepinephrine in albino and pigmented 15-day-old mice. In contrast, peripheral levels of dopamine were reduced only in albino TH-deficient mice and were higher in pigmented than in albino mice, regardless of the presence or absence of TH. We next examined age-related changes in dopamine and cutaneous expression of tyrosinase and melanin in albino and pigmented TH wild-type mice. We found that the differences in peripheral dopamine between pigmented and albino mice disappeared with advancing age following changes in expression and function of tyrosinase. In young animals, tyrosinase was present in epidermis but did not produce detectable melanin. With advancing age, tyrosinase was localized only around hair follicles, melanin synthesis became more pronounced, and dopamine synthesis decreased. The data reveal a previously unrecognized TH-independent major pathway of peripheral dopamine synthesis in young, but not adult, mice. The transient nature of this source of dopamine reflects a developmental switch in tyrosinase-dependent production of dopamine to production of melanin.
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PMID:Tyrosinase: a developmentally specific major determinant of peripheral dopamine. 1283 89

To understand the onset and the molecular mechanisms triggering dopaminergic (DA) dysregulation in Attention-Deficit Hyperactivity Disorder (ADHD), we have used the Spontaneously Hypertensive Rats (SHR), the most widely studied animal model for this disease. We have studied the pattern of expression of specific genes involved in DA neuron differentiation, survival and function during postnatal (P) development of the ventral midbrain in SHR males. Our results show that tyrosine hydroxylase and DA transporter gene expression are significantly and transiently reduced in the SHR midbrain during the first month of postnatal development, although with a different kinetic. The other genes analyzed do not show significant variation between SHR and control rats. In addition, high-affinity DA uptake activity is significantly reduced in synaptosomes obtained from the striatum of 1-month-old SHR, when compared to controls. Our data suggest that down-regulation of DA neurotransmission occurs in the midbrain of SHR in a developmentally regulated temporal window during postnatal development, thus strengthening the hypodopaminergic hypothesis in the pathogenesis of ADHD.
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PMID:Altered midbrain dopaminergic neurotransmission during development in an animal model of ADHD. 1462 10

Lactation deficiency may have important consequences on infant health, particularly in populations of low socioeconomic status. The OFA hr/hr (OFA) strain of rats, derived from Sprague-Dawley (SD) rats, has deficient lactation and is a good model of lactation failure. We examined the reproductive performance and hormonal profiles in OFA and SD strains to determine the cause(s) of the lactation failure of the OFA strain. We measured hormonal (PRL, GH, gonadotropins, oxytocin, and progesterone) levels by RIA in cycling, pregnant, and lactating rats and in response to suckling. Dopaminergic metabolism was assessed by determination of mediobasal hypothalamic dopamine and dihydroxyphenylacetic acid (DOPAC) concentrations by HPLC and tyrosine hydroxylase expression by immunocytochemistry and western blot. OFA rats have normal fertility but 50% of the litters die of malnutrition on early lactation; only 6% of the mothers show normal lactation. The OFA rats showed lower circulating PRL during lactation, increased hypothalamic dopamine and DOPAC, and impaired milk ejection with decreased PRL and oxytocin response to suckling. Before parturition, PRL release and lactogenesis were normal, but dopaminergic metabolism was altered, suggesting activation of the dopaminergic system in OFA but not in SD rats. The number of arcuate and periventricular neurons expressing tyrosine hydroxylase was higher in SD rats, but hypothalamic expression of TH was higher in OFA rats at the end of pregnancy and early lactation. These results suggest that the OFA rats have impaired PRL release linked with an augmented dopaminergic tone which could be partially responsible for the lactational failure.
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PMID:Hormonal profile and reproductive performance in lactation deficient (OFA hr/hr) and normal (Sprague-Dawley) female rats. 1750 26


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