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)

Striatal dopamine (DA) content, tyrosine hydroxylase (TH) activity, and total biopterin content were measured as parameters of recovery, after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in 7-week-old (young) and 28-week-old (older) C57 BL/6 mice. After 10 consecutive days of injection of MPTP (30 mg/kg/day) young mice were sacrificed at one day and 2, 4, 8, 12 and 20 weeks; older mice (20 mg/kg/day) at one day and 4, 8, and 12 weeks. All 3 parameters were markedly reduced one day after the last injection of MPTP. During the observation period, the parameters showed a gradual and partial recovery. The recovery rates of the 3 parameters differed significantly, especially during the early phases of 2-8 weeks. Total biopterin content showed a greater rate of recovery than TH activity and TH activity, a greater rate of recovery than DA content. In the older mice group, the recovery of all 3 parameters was retarded significantly, and dissociation of the recovery rates between the 3 parameters was more prominent. The results of our present study suggest that, following neurotoxic injury, the recovery of biopterin may play a significant role in dopaminergic terminal regeneration.
 ...
PMID:Difference in recovery patterns of striatal dopamine content, tyrosine hydroxylase activity and total biopterin content after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration: a comparison of young and older mice. 256 51

The effects of 3-acetylpyridine (3-AP) administration to rats on the mesotelencephalic dopamine system were assessed. A single 3-AP injection resulted in biochemical and immunohistochemical evidence of degeneration of the nigrostriatal dopamine system. Six weeks after 3-AP treatment decreases in both striatal dopamine content and the activity of the catecholamine biosynthetic enzyme tyrosine hydroxylase were observed. Immunohistochemical examination suggested a decreased density of striatal tyrosine hydroxylase-immunoreactive fibers and revealed the emergence of a distinctly patchy organization of the dopamine innervation to the dorsolateral striatum. While 3-AP administration resulted in biochemical and anatomical data consistent with the degeneration of nigrostriatal dopamine fibers, no significant changes in dopamine content or the density or pattern of tyrosine hydroxylase-immunoreactive fibers in the anteromedial prefrontal cortex or nucleus accumbens were seen. These data suggest that 3-AP administration may result in a relatively specific degeneration of the nigrostriatal dopamine system. Since 3-AP causes both a profound loss of the climbing fiber input to the cerebellum derived from the inferior olivary nucleus, and the degeneration of nigrostriatal dopamine neurons, 3-AP administration may provide a useful model of olivopontocerebellar atrophy-associated parkinsonism. Moreover, the differences in the neurotoxicity caused by 3-AP and that elicited by another pyridine which causes striatal dopamine depletion (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP) may offer important insights into the mechanisms of both species- and site-specific pyridine neurotoxins.
 ...
PMID:3-Acetylpyridine-induced degeneration of the nigrostriatal dopamine system: an animal model of olivopontocerebellar atrophy-associated parkinsonism. 256 69

Adult beagle dogs of either sex were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-HCl (2.5 mg/kg, i.v.) alone or after pretreatment with pargyline (5.0 mg/kg, s.c., twice), with pargyline alone, or were uninjected. Groups were killed 2 h, 3 weeks, or 3 months after injection, and several brain areas were assayed for biogenic amines and their synthetic and degradative enzymes. MPTP caused a massive and permanent loss of striatal dopamine, tyrosine hydroxylase, and 3,4-dihydroxyphenylalanine decarboxylase activities and the loss of cells within the substantia nigra pars compacta. Dopamine and norepinephrine also were depleted to various degrees in cortex, olfactory bulb, and hypothalamus; however, dopamine beta-hydroxylase activity in cortex was normal. There was no cell loss in the ventral tegmental area or locus ceruleus. The activities of monoamine oxidase (MAO)-A and MAO-B in cortex and caudate were not affected by MPTP. Despite a permanent loss of the nigrostriatal system, the dogs exhibited only a transient hypokinesia lasting 1-2 weeks. Pargyline pretreatment prevented the loss of striatal dopamine and cells from the substantia nigra, but did not prevent a prolonged but reversible decrease in the concentration of dopamine metabolites. It is argued that this apparent inhibition of MAO is due not to suicide inactivation of the enzyme by MPTP, but to reversible inhibition by accumulation of the pyridinium metabolite, 1-methyl-4-phenylpyridinium, selectivity in aminergic terminals.
 ...
PMID:Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the dog: effect of pargyline pretreatment. 256 5

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its main metabolite 1-methyl-4-phenylpyridinium ion (MPP+) on the peripheral catecholaminergic system of the rat were investigated. MPTP and MPP+ injections (20 mg/kg i.p.) caused a marked acute depletion of heart noradrenaline, up to 75% twelve hours after the administration, and a decrease of adrenal gland adrenaline. The time-course of the effect of MPTP and MPP+ is reported, together with a decrease in the tyrosine hydroxylase activity after MPTP treatment, more evident in the adrenal glands. Pargyline (50 mg/kg i.p.) is not able to prevent such a neurotoxic peripheral effect.
 ...
PMID:Acute peripheral catecholaminergic changes in rat after MPTP and MPP+ treatment. 257 Apr 48

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a neurotoxin producing parkinsonism, causes an obvious reduction in tyrosine hydroxylase (TH) activity in the caudate nucleus. This depletion of TH activity is due to degeneration of TH-positive punctate dopaminergic terminals. The disappearance of these terminals unmasks the presence of long branching, varicose preterminal fibers, which may be sprouting after degeneration of their terminal arborizations. Glial cells, normally sparse with delicate processes, undergo intense increase in number and a robust hypertrophy. All of these changes are prevented completely by administration of deprenyl, a monoamine oxidase inhibitor, before and after MPTP. These neuropathological effects are additional manifestations of the dopaminergic neurotoxicity induced by MPTP. The metabolism of MPTP, which is blocked by monoamine oxidase inhibition, is apparently necessary for the expression of toxicity in the brain by this neurotoxin.
 ...
PMID:Neuropathological changes in the caudate nucleus elicited by MPTP and their prevention by monoamine oxidase inhibition. 257 4

We have previously reported that ethanol and acetaldehyde potentiate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice, enhancing dopamine (DA) depletion in the striatum. The present study was designed to determine whether such enhancement of neurotoxicity was specific for the nigro-striatal DA pathway. In 5-week-old mice acetaldehyde treatment did not enhance DA depletion seen 7 days after MPTP treatment. In 8-week-old animals, however, acetaldehyde or ethanol given with MPTP decreased striatal DA content to about 10% of controls, whereas the depletion was to 43% of controls when MPTP was given alone. In acetaldehyde or ethanol and MPTP-treated mice, changes in DA levels were observed only in the striatum. DA contents in the hypothalamus, olfactory bulb and frontal cortex were similar to that in controls. Contents of norepinephrine and serotonin in striatum, hypothalamus, olfactory bulb and cerebral cortex were not affected by any of the treatments. Three months after MPTP alone, striatal DA recovered to 74% of controls in 8-week-old mice, whereas no recovery occurred in acetaldehyde and MPTP-treated mice. Moreover, both tyrosine hydroxylase (TH) immunocytochemistry and Cresyl violet staining showed an extensive and selective cell loss in the pars compacta of the substantia nigra (SNc) of the mice treated with acetaldehyde or ethanol and MPTP, whereas MPTP alone caused only a limited cell degeneration.
 ...
PMID:MPTP treatment combined with ethanol or acetaldehyde selectively destroys dopaminergic neurons in mouse substantia nigra. 257 5

Changes in striatal dopamine (DA) neurochemistry, tyrosine hydroxylase immunocytochemistry of DA fibers, and behavior following the combined administration of diethyldithiocarbamate (DDC) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice were assessed. The combined treatment of DDC and MPTP produced a dose-dependent decrease in striatal DA levels and a dose-related increase in the striatal DOPAC:DA ratio. Cumulative doses of MPTP equal to or exceeding 53.0 (26.5 mg/kg x 2. i.p.), given in combination with DDC, were effective in reducing striatal DA levels to less than 25% of control levels 2 weeks after treatment. Tyrosine hydroxylase immunocytochemistry revealed large deafferentation of DA terminal regions in striatum, moderate reductions in nucleus accumbens and dendritic regions of substantia nigra, and slight reductions in the number of DA cell bodies in substantia nigra. Mice treated with DDC and MPTP became hyperactive during the light phase of their diurnal cycle: psychopharmacological data suggest that postsynaptic DA receptors were supersensitized following this treatment. These data provide evidence that the combined treatment of DDC and MPTP produces severe and enduring depletion of mesostriatal DA, and also concomitant behavioral changes in mice.
 ...
PMID:Morphological, neurochemical, and behavioral characterizations associated with the combined treatment of diethyldithiocarbamate and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. 257 5

Immunohistochemical studies of monoamine neurons were performed to evaluate toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on young adult mice and compare them with those of their offspring. Mice, 9-11 weeks old (C57BL/6J), injected subcutaneously with a large dose of MPTP (17 mg/kg per day) during pregnancy on Day 9 and 12 of gestation (G9 and G12) miscarried and were examined at 13 weeks of age. Conversely, mice treated during pregnancy with sequential low dose of MPTP (2.8 mg/kg per day at G9-G17 for 8 days) successfully delivered their babies and were examined at the age of 15 weeks. Baby mice were examined at 1 and 6 weeks of age. The tyrosine hydroxylase-, aromatic L-amino acid decarboxylase- and dopamine (DA)-immunoreactive density of caudoputamen was reduced in 13-week-old mice treated with high dose of MPTP but not in the 15-week-old mothers exposed to a low dose of MPTP as compared to their respective controls. The DA-immunoreactive density of the caudoputamen was the only staining that was reduced in both 1- and 6-week-old baby mice. In conclusion, these results demonstrate that MPTP injected to pregnant mice causes a DA depletion in the striatum of their offspring indicating a transplacental effect of MPTP. The findings also indicate that fetal brain is more susceptible to MPTP toxicity than the brain of young pregnant mice.
 ...
PMID:Transplacental effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on brain dopaminergic neurons in the mouse. An immunohistochemical study. 257 40

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to young (2-3 months) and aging (12 months) C57BL/6 mice (4 x 20 mg/kg, i.p., given 12 h apart) reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum, and reduced dopamine (DA) concentration to 28% of controls in young, and 16% of controls in aging mouse brain five weeks after administration. Although GM1 ganglioside treatment (30 mg/kg, i.p., daily for 5 weeks) restored striatal dopamine concentration to 74% of the control concentration in young mice, such an apparent recovery was not seen in aging brain. Immunocytochemical analysis also showed marked recovery of TH-IR fibers in the striatum of MPTP-depleted young mice treated with GM1 ganglioside while TH-IR fibers in the striatum of MPTP-depleted aging mice showed no recovery with such treatment. We conclude that treatment of MPTP-depleted young mice with GM1 ganglioside results in partial recovery in the striatal DA system, but such benefits do not extend to aging mice.
 ...
PMID:Exogenous GM1 gangliosides induce partial recovery of the nigrostriatal dopaminergic system in MPTP-treated young mice but not in aging mice. 260 83

Dopaminergic rat mesencephalic neurons in culture were exposed to a group of potential environmental neurotoxins. These cultures, which contained 0.5 to 1% dopaminergic neurons, were a suitable tool for determining nonselective and selective dopaminergic cytotoxicity. Selective toxicity was quantitated as the concentration which destroyed half of the population of dopaminergic neurons as visualized by tyrosine hydroxylase immunocytochemistry. Nonselective toxicity was defined as the concentration of test drug which destroyed half of the entire population of cultured cells as visualized by phase contrast microscopy. The compounds tested were selected to fulfill two molecular criteria underlying the toxic activity of 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toward dopaminergic cells: 1) to be a substrate for the selective uptake system of the dopaminergic neurons and 2) to possess a delocalized positive charge related to their ability to inhibit mitochondrial electron transport. Of a total number of 29 compounds tested, MPP+ and its close derivatives, 2'-methyl-MPP+ and p-amino-MPP+, exhibited highly selective dopaminergic toxicity, hence the requirements for a selective dopaminergic neurotoxin are rather strict.
 ...
PMID:Toxic effects of potential environmental neurotoxins related to 1-methyl-4-phenylpyridinium on cultured rat dopaminergic neurons. 278 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>