Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brains from Cebus Apella monkeys have been mapped biochemically using a cryo-section technique which enables exact micro-dissectioning of tissue. Two neurotransmitters; noradrenaline (NA) and gamma-amino-butyric acid (GABA) were measured by gas chromatography-masspectrometry technique. In addition biochemical markers reflecting metabolic activity in the dopamine (homovanillic acid, HVA, 3, 4-dihydroxyphenylacetic acid, DOPAC), serotonin (5-hydroxyindoleacetic acid, 5-HIAA), noradrenaline (4-hydroxy-3-methoxy-phenylglycol, HMPG), acetylcholine (choline acetyltransferase, CAT) and GABA (glutamic acid decarboxylase, GAD) transmitter systems were assayed. The distribution of these transmitter markers roughly corresponded to earlier studies in other non-human primates, whereas similar studies on the human brain generally show lower concentrations and enzyme activities. One monkey exposed to severe stress immediately before death deviated from the normal animals with regard to HVA, 5-HIAA, GAD and GABA. For the study of neuroleptic drugs, and notably their neurological side-effects, Cebus Apella monkeys have turned out to be particularly useful. In our laboratory we have employed this species of monkey to develop a model for acute dystonia and tardive dyskinesia (Gunne and Barany 1976, 1979, Barany et al. 1979). As a first step in the topological mapping of brain neuro-chemistry in these animals we here present data from normal monkeys, not treated with neuroleptics. During the ongoing project there was an unplanned "stress experiment" in one monkey, which had a nightly fight with a cage partner and had to be sacrificed the morning after due to severe wounds. The present communication describes a method for obtaining well-defined samples from monkey brains and presents the data on homovanillic acid (HVA), 3.4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NA), 4-hydroxy-3-methoxy-phenyl glycol (HMPG), choline acetyltransferase (ChAT), glutamic acid decarboxylase (GAD), and gamma-amino-butyric acid (GABA) in discrete regions from 7 drug-naive control monkeys. Also data from the stressed animal are presented.
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PMID:Discrete regional distribution of biochemical markers for the dopamine, noradrenaline, serotonin, GABA and acetylcholine systems in the monkey brain (Cebus Apella). Effects of stress. 615 Jun 1

The Rett syndrome (RS) is a peculiar, sporadic, atrophic disorder, almost entirely confined to females. After the first six months of life there is developmental slowing with reduced communication and head growth for about one year. This is followed by a rapid destructive stage with severe dementia and loss of hand skills (with frequent hand wringing), apraxia and ataxia, autistic features and irregular breathing with hyperventilation. Seizures often supervene. Subsequently there is some stabilization in a pseudo-stationary stage during the preschool to school years, associated with more emotional contact but also abnormalities of the autonomic and skeletal systems. After the age of 15-20 years, a late motor deterioration occurs with dystonia and frequent spasticity but seizures become milder. RS has generally been considered an X-linked disorder in which affected females represent a new mutation, with male lethality. Linkage studies suggested a critical region at Xq28. In 1999, mutations in the gene MECP2 encoding X-linked methyl cytosine-binding protein 2 (MeCP2) were found in a proportion of Rett girls. This protein can bind methylated DNA. Analyses are leading to much further investigation of mutants and their effects on genes. Neuropathological and electrophysiological studies of RS are described. Description of neurometabolic factors includes reduced levels of dopamine, serotonin, noradrenaline and choline acetyltransferase (ChAT) in brain, also estimation of nerve growth factors, endorphin, substance P, glutamate and other amino acids and their receptor levels. The results of neuroimaging are surveyed, including volumetric magnetic resonance imaging (MRI) and positron emission tomography (PET).
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PMID:Rett syndrome: review of biological abnormalities. 1125 89

The underlying pathophysiological mechanisms of hereditary types of paroxysmal dyskinesias are still unknown, but basal ganglia dysfunctions seem to play a critical role. In fact, numerous pharmacological, neurochemical, immunohistochemical and electrophysiological investigations in the dt(sz) hamsters, a unique rodent model of age-dependent primary paroxysmal dystonia, revealed alterations within the basal ganglia, particularly of the GABAergic and dopaminergic neurotransmitter systems. A deficit in several types of striatal GABAergic interneurons in dt(sz) mutant hamsters seems to play a crucial pathophysiological role, but deficits in other types of striatal interneurons cannot be excluded by previous studies. In view of ameliorating effects of anti-cholinergic drugs in dystonic patients, we therefore investigated the density of striatal cholinergic interneurons in the present study. These interneurons were marked specifically by the enzyme choline acetyltransferase and counted by using a stereological counting method in a blinded fashion. Additionally, acetylcholine receptor binding was determined in mutant and nondystonic control hamsters by autoradiographic analyses with the nonselective muscarinic ligand [(3)H]-quinuclidinyl benzilate (QNB) in 11 brain (sub)regions. There were no significant differences in the density of striatal cholinergic interneurons between dt(sz) mutant hamsters (789 +/- 39 interneurons/mm(3)) and nondystonic controls (807 +/- 36 interneurons/mm(3)). [(3)H]QNB binding was also comparable between mutant and control hamsters. These results point to an unaltered striatal cholinergic neurotransmitter system in dt(sz) hamsters under basal conditions.
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PMID:Acetylcholine receptor binding and cholinergic interneuron density are unaltered in a genetic animal model of primary paroxysmal dystonia. 1676 32

The dystonias are comprised of a group of disorders that share common neurological abnormalities of involuntary twisting or repetitive movements and postures. The most common inherited primary dystonia is DYT1 dystonia, which is due to loss of a GAG codon in the TOR1A gene that encodes torsinA. Autopsy studies of brains from patients with DYT1 dystonia have revealed few abnormalities, although recent neuroimaging studies have implied the existence of microstructural defects that might not be detectable with traditional histopathological methods. The current studies took advantage of a knock-in mouse model for DYT1 dystonia to search for subtle anatomical abnormalities in the striatum, a region often implicated in studies of dystonia. Multiple abnormalities were identified using a combination of quantitative stereological measures of immunohistochemical stains for specific neuronal populations, morphometric studies of Golgi-stained neurons, and immuno-electron microscopy of synaptic connectivity. In keeping with other studies, there was no obvious loss of striatal neurons in the DYT1 mutant mice. However, interneurons immunoreactive for choline acetyltransferase or parvalbumin were larger in the mutants than in control mice. In contrast, interneurons immunoreactive for neuronal nitric oxide synthase were smaller in the mutants than in controls. Golgi histochemical studies of medium spiny projection neurons in the mutant mice revealed slightly fewer and thinner dendrites, and a corresponding loss of dendritic spines. Electron microscopic studies showed a reduction in the ratio of axo-spinous to axo-dendritic synaptic inputs from glutamatergic and dopaminergic sources in mutant mice compared with controls. These results suggest specific anatomical substrates for altered signaling in the striatum and potential correlates of the abnormalities implied by human imaging studies of DYT1 dystonia.
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PMID:Subtle microstructural changes of the striatum in a DYT1 knock-in mouse model of dystonia. 2333 80