Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the involvement of catecholamines and/or the cyclic AMP (cAMP) systems in the development of drug dependence, we examined whether morphine dependence was developed in tyrosine hydroxylase (TH) heterozygous (TH+/-) and cAMP response element binding protein (CREB) binding protein (CBP) heterozygous (CBP+/-) mice. Morphine (10 mg/kg) induced place preference in the wild-type mice. In the TH+/- and CBP+/- mice, however, we could not find any morphine-induced place preference. When the wild-type mice pretreated with morphine (10 mg/kg) twice a day for 5 days were challenged with naloxone (5 mg/kg), they showed increased numbers of jumping, rearing and forepaw tremor as a sign of withdrawal symptom and increased level of cAMP in the thalamus/hypothalamus, but not in the striatum. However, increased numbers of jumping and forepaw tremor in the TH+/- and CBP+/- mice and increased level of cAMP in the thalamus/hypothalamus of TH+/- mice were not observed. These results suggest that catecholamines and CBP are involved in the development of morphine dependence, and that some changes in the catecholaminergic and/or cAMP system induced by repeated morphine treatment play an important role in the addiction of morphine.
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PMID:[The mechanisms of morphine dependence and it's withdrawal syndrome: study in mutant mice]. 1123 92

The frissonnant (fri) mutation is an autosomic recessive mutation which spontaneously appeared in the stock of C3H mice. fri mutant mice have locomotor instability and rapid tremor. Since tremor ceases when mutant mice have sleep or are anaesthetized, and because of their obvious stereotyped motor behavior, these mice could represent an inherited Parkinsonian syndrome. We show here that the fri/fri mouse fulfills two out of the three criteria required to validate an experimental model of human disease, that is isomorphism, homology and predictivity. Indeed, fri/fri mice present an important motor deficit accompanying visible tremor and stereotypies. They display some memory deficits as in human Parkinson's desease. l-Dopa and apomorphine (dopaminergic agonists), ropinirole (selective D2 agonist), and selegiline (an monoamino-oxidase B [MAO-B] inhibitor) improve their clinical status. However, neither anatomopathological evidence of nigrostriatal lesion, nor decrease in tyrosine hydroxylase production could be seen.
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PMID:The frissonnant mutant mouse, a model of dopamino-sensitive, inherited motor syndrome. 1144 53

Inborn errors of catecholamine biosynthesis are rare but of great interest as they are genetic disorders, and in some, treatment may completely reverse severe neurological abnormalities. They also provide insights into the action of the biogenic amines in the developing brain. We describe the clinical course of an infant with tyrosine hydroxylase (TOH) deficiency over a 30-month period. The parents are consanguineous, and genetic analysis revealed the infant to be homozygous for the common G698A mutation in the TOH gene. TOH deficiency can be seen as a model of pure catecholamine deficiency. Experimental evidence, reports of other disorders of biogenic amines, and our experience with this infant suggest that the symptoms of catecholamine deficiency in infancy can be broadly subdivided. Signs of dopamine deficiency include tremor, hypersensitivity to levadopa (L-dopa) therapy, oculogyric crises, akinesia, rigidity, and dystonia. Manifestations of norepinephrine deficiency include ptosis, miosis, profuse oropharyngeal secretions, and postural hypotension. Hypersensitivity to L-dopa was a particular management problem in this infant.
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PMID:Tyrosine hydroxylase deficiency: clinical manifestations of catecholamine insufficiency in infancy. 1192 Nov 23

Overt behavioral symptoms of Parkinson's disease (PD) do not occur until over 80% of the striatal dopamine content has been lost. Diagnosis of the disorder relies on identifying clinical symptoms including akinesia, resting tremor, and rigidity. In retrospect, behavioral deficits are observed several years prior to diagnosis. Behavioral manifestations in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, such as changes in general locomotor activity and rotorod performance, require large doses of MPTP and are often transient. We hypothesized that, as in PD, subtle behavioral changes also occur in the MPTP model. In this paper, we demonstrate that mice treated with moderate doses of the dopaminergic toxin MPTP display deficits in behavioral parameters that are significantly correlated with the loss of striatal dopamine. In addition, these behavioral measures are correlated to dopamine transporter, vesicular monoamine transporter, and tyrosine hydroxylase expression and are improved following L-DOPA administration. Detection of dopamine-modulated behavioral changes in moderately depleted MPTP mice will allow for more efficacious use of this model in PD research.
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PMID:Detection of behavioral impairments correlated to neurochemical deficits in mice treated with moderate doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 1246 Jun 10

Alpha-synuclein is a major component of Lewy bodies (LBs) in the substantia nigra and cortex in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and in glial inclusions in multiple systems atrophy (MSA). Mutations in alpha-synuclein have been associated with autosomal dominant forms of PD. We investigated the clinical and neuropathological effects of overexpression of human alpha-synuclein, alpha-synuclein A30P, and alpha-synuclein A53T under the control of the hamster prion protein (PrP) promoter; 5-15x endogenous levels of protein expression were achieved with widespread neuronal, including nigral, transgene expression. High expression of alpha-synuclein A30P in the Tg5093 line was associated with a progressive motor disorder with rigidity, dystonia, gait impairment, and tremor. Histological analysis of this line showed aberrant expression of the protein in cell soma and progressive CNS gliosis, but no discrete Lewy body-like alpha-synuclein inclusions could be identified. Biochemical analysis demonstrated alpha-synuclein fragmentation. Despite strong expression of the transgene in the nigra, there was no specific deterioration of the nigrostriatal dopaminergic system as assessed by quantitation of nigral tyrosine hydroxylase (TH) containing neurons, striatal TH immunoreactivity, dopamine levels, or dopamine receptor number and function. Lower expressing lines had no specific behavioral or histopathological phenotype. Thus, high expression of mutant human alpha-synuclein resulted in a progressive motor and widespread CNS gliotic phenotype independent of dopaminergic dysfunction in the Tg5093 line.
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PMID:Motor dysfunction and gliosis with preserved dopaminergic markers in human alpha-synuclein A30P transgenic mice. 1249 58

We administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to adult, male cats to model Parkinson's disease (PD), and utilized proton magnetic resonance imaging (MRI) and spectroscopy (MRS) at a field strength of 1.5 T to identify metabolic degenerative changes in the striatum in vivo. Neurologic status and somatosensory-evoked potentials in vivo, as well as postmortem striatal histopathological and immunohistochemical parameters, were examined. Nine cats were equally divided into three groups and treated daily for 10 days as follows: saline, MPTP, and pargyline (a monoamine oxidase inhibitor) plus MPTP. The MPTP-treated cats displayed bradykinesia, head tremor, and reduced oculovestibular reflex activity. MRI showed a diffuse increase of the T2-weighted signal in the striatum of two MPTP-treated cats. Analysis of the MRS spectra indicated significantly lower N-acetylaspartate/creatine (CR) and glutamine-glutamate complex/CR ratios than the control baseline. Two MPTP-treated cats had low choline-containing compounds/CR ratio, whereas a lactate peak was present in all MPTP-treated cats. In the striatum of the MPTP-treated cats, there was a significant decline of tyrosine hydroxylase immunoreactivity and histological evidence for a diffuse cytotoxic reaction. Pretreatment with pargyline attenuated the MPTP-induced clinical signs, MRI and MRS changes, and the histopathological and immunoreactivity alterations. We conclude that proton MRI/MRS is a sensitive, noninvasive measure of neural toxicity and biochemical alteration of the striatum in a feline model of PD.
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PMID:Proton magnetic resonance imaging and spectroscopy identify metabolic changes in the striatum in the MPTP feline model of parkinsonism. 1261 22

Neural progenitor cells existing in the developing and adult brain retain the capacity to self renew and to produce the major cell types of the brain opening new avenues for restorative therapy of neuropsychiatric disorders. These cells can be grown in vitro while retaining the potential to differentiate into nervous tissue. A primary target for neurorestoration is Parkinson's disease, characterized by a continuous loss of the dopaminergic neurons in the substantia nigra pars compacta leading to dopamine depletion in the striatum and subsequent clinical symptoms including bradykinesia, rigidity and tremor. We established a protocol for long-term expansion and dopaminergic differentiation of rodent and human mesencephalic neural progenitor cells. Here we perform functional studies using both biochemical and electrophysiological techniques on dopaminergic neurons derived from rodent mesencephalic progenitor cells labeled with tyrosine hydroxylase (TH) gene promotor-driven expression of enhanced green fluorescence protein (EGFP). Thus, we demonstrate that these cells produce and release dopamine, express voltage-gated potassium and sodium currents, and fire action potentials. Furthermore, we detect a slowly activating hyperpolarization-activated inward cation current (I(h)), which is specific for dopaminergic neurons among present midbrain neurons. Our results demonstrate that differentiated mesencephalic progenitors exhibit some major morphological and functional characteristics of dopaminergic neurons. Therefore, these neural progenitor cells might serve as a useful source of dopaminergic neurons for studying the development and degeneration of these cells and may further serve as a continuous, on-demand source of cells for therapeutic transplantation in Parkinson's disease.
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PMID:Functional characterization of dopaminergic neurons derived from rodent mesencephalic progenitor cells. 1459 63

Parkinson's disease, a major neurodegenerative disorder in humans whose etiology is unknown, may be associated with some environmental factors. Nocardia otitidiscaviarum (GAM-5) isolated from a patient with an actinomycetoma produced signs similar to Parkinson's disease following iv injection into NMRI mice. NMRI mice were infected intravenously with a non-lethal dose of 5 x 10(6) colony forming units of N. otitidiscaviarum (GAM-5). Fourteen days after bacterial infection, most of the 60 mice injected exhibited parkinsonian features characterized by vertical head tremor, akinesia/bradykinesia, flexed posture and postural instability. There was a peak of nocardial growth in the brain during the first 24 h followed by a decrease, so that by 14 days nocardiae could no longer be cultured. At 24 h after infection, Gram staining showed nocardiae in neurons in the substantia nigra and occasionally in the brain parenchyma in the frontal and parietal cortex. At 21 days post-infection, tyrosine hydroxylase immunolabeling showed a 58% reduction of tyrosine hydroxylase in the substantia nigra, and a 35% reduction of tyrosine hydroxylase in the ventral tegmental region. Dopamine levels were reduced from 110 +/- 32.5 to 58 +/- 16.5 ng/mg protein (47.2% reduction) in brain from infected mice exhibiting impaired movements, whereas serotonin levels were unchanged (191 +/- 44 protein in control and 175 +/- 39 ng/mg protein in injected mice). At later times, intraneuronal inclusion bodies were observed in the substantia nigra. Our observations emphasize the need for further studies of the potential association between Parkinson's disease or parkinsonism-like disease and exposure to various nocardial species.
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PMID:Nocardia otitidiscaviarum (GAM-5) induces parkinsonian-like alterations in mouse. 1506 17

Parkinson's disease is characterized by bradykinesia, rigidity and a resting tremor and the underlying basis for those symptoms is the loss of dopaminergic cells in the nigrostriatal system. Similar to PD, an age-related decrease locomotor activity and the expression of tyrosine hydroxylase immunoreactivity has been observed in rhesus monkeys, but the reason for this decrease in dopaminergic function remains to be elucidated. Trophic factors such as glial cell line derived neurotrophic factor (GDNF) and neurturin sustain the dopaminergic phenotype in midbrain neurons and act through a common receptor tyrosine kinase (RET). Examination of RET expression by immunohistochemistry was performed on sections of tissue containing the substantia nigra pars compacta of young, middle, and old aged rhesus monkeys. Stereological estimates of the number and cellular area of RET-immunoreactive cells found no change with age. Estimation of changes in RET protein using fluorescence intensity measurement was also similar across age groups. The results indicate that the mechanisms of GDNF and neurturin signaling remain intact with age, and therefore these trophic factors may be able to enhance the dopaminergic function of neurons in the nigrostriatal system, when administered to individuals of any age.
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PMID:RET expression does not change with age in the substantia nigra pars compacta of rhesus monkeys. 1595 Mar 22

The authors present four cases from two unrelated families with young-onset predominant cervical dystonia with a dramatic sustained response to levodopa. Onset age was 12 years (range 9 to 15). Additional symptoms included postural hand tremor and laryngeal dystonia. Genetic testing for GTP cyclohydrolase I, tyrosine hydroxylase, and sepiapterin reductase was negative. These cases may represent new forms of dopa-responsive dystonia. Levodopa is advisable in all patients with young-onset cervical dystonia.
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PMID:Familial dopa-responsive cervical dystonia. 1650 23


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