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

Somatostatin was measured in CSF from individuals with a variety of neurologic diseases. In ventricular CSF, somatostatin concentration was significantly lower in individuals with childhood-onset dystonia than in individuals with other forms of dystonia or with other disorders. Severity of childhood dystonia correlated with somatostatin concentration, suggesting a progressive dysfunction of somatostatin-containing neurons with increasing disease severity. There were no significant differences in somatostatin concentration in lumbar CSF. Multiple forms of immunoreactive somatostatin were found in a pool of lumbar CSF from normal individuals. Labeled somatostatin administered intra-arterially to rats failed to cross the blood-brain barrier.
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PMID:Ventricular fluid somatostatin concentration decreases in childhood-onset dystonia. 286 69

It has been reported that intraventricular injection of chlorpromazine methiodide (CPZMI), a quaternary ammonium derivative of chlorpromazine, in rats induces abnormal, twisting postures which may serve as an experimental model of the human movement disorder dystonia. We have shown elsewhere that the behavior induced by intraventricular CPMZI is identical to what has been called "barrel rotation," first observed to follow intraventricular injection of somatostatin (SRIF), which consists of twisting about the long axis, with repetitive lateral rolling. The suitability of barrel rotation, induced by CPZMI or SRIF, as an experimental model for dystonia depends on its physiologic basis. Human dystonia is clinically not a convulsive phenomenon. SRIF-induced barrel rotation has been reported to be associated with epileptiform activity recorded by the electroencephalogram (EEG). The purpose of this study was to investigate EEG activity during CPZMI- and SRIF-induced rotation. We found that CPZMI barrel rotation was not associated with epileptiform activity in cortex, amygdala, or hippocampus, and contrary to prior reports, neither was SRIF rotation. Both CPZMI and SRIF injected in high doses could induce epileptiform activity, but this was associated with clonic motor phenomena and not barrel rotation. We conclude that electroencephalographic criteria do not exclude either CPZMI- or SRIF-induced rotation as models for movement disorders, but their validity as such requires further study.
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PMID:Electroencephalographic studies of chlorpromazine methiodide and somatostatin-induced barrel rotation in rats. 613 Sep 62

Barrel rotation is a unique motor response observed in rats in which, following an intracerebral injection, the animal develops a twist about the long axis and rolls laterally repeatedly. The response was first described following injection of somatostatin. We have previously shown that 'experimental dystonia' in rats induced by intraventricular chlorpromazine methiodide (CPZMI) is identical to barrel rotation, and that it is due to an antimuscarinic effect. The purpose of the present study was to investigate the neuroanatomical basis of CPZMI-induced rotation. We injected CPZMI in 3 microliters into right lateral and IVth ventricle and found that IVth ventricle injections were significantly more likely to induce rotation. Nuclear groups adjacent to the IVth ventricle, which are rich in muscarinic cholinergic receptors, include locus coeruleus and vestibular nuclear complex (VNC). We found that only VNC injections induced rotation. Only certain control compounds injected into VNC elicited the response. We conclude that barrel rotation has a specific neuroanatomical basis, involving central vestibular mechanisms, and that it has a specific pharmacologic basis.
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PMID:Chlorpromazine methiodide acts at the vestibular nuclear complex to induce barrel rotation in the rat. 666 22

In the dt(sz) mutant hamster with idiopathic generalized dystonia, functional abnormalities of several neurotransmitters have been suggested to play a role in the development of symptoms. In the present study, we have used histochemistry with (35)S-ATP labeled oligonucleotides to determine whether these abnormalities are associated with modulation in the expression of neurotransmitter genes in motor regions. We examined the expression of genes encoding cholecystokinin (CCK), somatostatin (SRIF), thyrotropin-releasing hormone (TRH), glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43) in the cortex and basal ganglia of dystonic hamsters and of non-dystonic control hamsters of a related inbred line and of a non-related outbred line. The distribution of these mRNAs in normal hamster brain was similar to that in normal rat brain. In all cortical regions studied (frontal, parietal and piriformis), the expression of CCK was similar in dystonic and inbred controls but was significantly greater than in outbred controls. In the anterior thalamus, CCK expression was lower in dystonic hamsters than in both control groups. SRIF expression was significantly decreased in the cortex and striatum of dystonic animals than in inbred and outbred control hamsters. GAD expression was lower in the striatum and substantia nigra, pars reticulata of dystonic than in outbred hamsters, but similar values were found in all groups in the other regions studied. TH was lower in the substantia nigra of dystonic than in inbred controls. No changes were found in GAP43 expression. This study demonstrates that changes in modulation of the expression of some peptides and neurotransmitter enzymes can be found in the dystonic hamster, which is in contrast to other animal models such as the dystonic rat, where no such changes have been found. The present data are consistent with previous findings in dt(sz) hamsters that suggest a dysfunction within the basal ganglia-thalamocortical circuits.
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PMID:Expression of cholecystokinin, somatostatin, thyrotropin-releasing hormone, glutamic acid decarboxylase and tyrosine hydroxylase genes in the central nervous motor systems of the genetically dystonic hamster. 1055 May 8

Mammalian motor activity displays circadian patterns in normal behaviour and in many movement disorders, like levodopa responsive dystonia and Parkinson's disease. Here, we hypothesized that a circadian pattern of dopamine synthesis would trigger rhythms in the expression of genes in regions receiving dopaminergic innervation. Indeed tyrosine hydroxylase and cholecystokinin mRNA were upregulated in the substantia nigra and ventral tegmental area in the course of the day. However, in the caudate putamen, the mRNA levels, for dopamine D2 and adenosine 2A receptor, dynorphin, and substance P were lower during the day than during the night, whereas the expression of dopamine D1 receptor, enkephalin, and somatostatin was stable. In the frontal cortex, a clear midday peak of enkephalin expression was detected, while cholecystokinin and vasoactive intestinal peptide expression did not vary. Clear circadian gene expression patterns can therefore be demonstrated in brain regions involved in motor regulation, but they do not follow a simple dopaminergic drive and more complex regulatory patterns have to be assumed.
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PMID:Circadian patterns of neurotransmitter related gene expression in motor regions of the rat brain. 1501 24

Primary dystonia is a common movement disorder with an unknown pathophysiology, but basal ganglia dysfunctions seem to play a critical role. Previous studies in the dtsz mutant hamster, an animal model of primary paroxysmal dystonia, demonstrated a deficit of striatal gamma-amino-butyric acid (GABA) containing interneurons, which normalized at the age of the spontaneous remission of the symptoms. Whereas the reduction of striatal parvalbumin-reactive interneurons is thought to be critically involved in the pathogenesis of dystonia in the hamster mutant, the impact of a reduced density of nitric oxide synthase (NOS) reactive interneurons within the striatum is still unclear. Beside GABA, these interneurons contain somatostatin, neuropeptide Y, nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and neuronal NOS, an enzyme which produces NO after the activation of the interneurons. In order to clarify if the reduced density of NOS-reactive interneurons contributes by an altered striatal production of nitric oxide (NO) to the occurrence of dystonic attacks in the hamster mutant, we performed microinjections of the NOS inhibitors 7-nitroindazole (7-NI) and Nomega-propyl-L-arginine (NPLA) and of the precursor of NO, L-arginine, into the striata of dtsz hamsters. Neither 7-NI (0.1 and 0.4 microg per hemisphere) and NPLA (2.5, 5 and 7.5 microg per hemisphere) nor L-arginine (9 and 18 microg per hemisphere) exerted any effects on the severity of dystonic movements in the dtsz mutant. Therefore, a critical involvement of striatal changes of NO in the pathophysiology of dystonic attacks in the dtsz hamster cannot be confirmed by the results of these pharmacological examinations. In view of the ontogenetic reduction of the other types of GABAergic interneurons, the deficit of NOS-reactive interneurons is possibly due to the same underlying unknown mechanism, but is less important for the pathophysiology of primary paroxysmal dystonia in the dtsz hamster mutant.
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PMID:Striatal microinjections of nitric oxide synthase inhibitors and L-arginine fail to exert effects on paroxysmal dystonia in the dtsz mutant. 1642 62

Although dystonia represents a major source of motor disability in Huntington's disease (HD), its pathophysiology remains unknown. Because recent animal studies indicate that loss of parvalbuminergic (PARV+) striatal interneurons can cause dystonia, we investigated if loss of PARV+ striatal interneurons occurs during human HD progression, and thus might contribute to dystonia in HD. We used immunolabeling to detect PARV+ interneurons in fixed sections, and corrected for disease-related striatal atrophy by expressing PARV+ interneuron counts in ratio to interneurons co-containing somatostatin and neuropeptide Y (whose numbers are unaffected in HD). At all symptomatic HD grades, PARV+ interneurons were reduced to less than 26% of normal abundance in rostral caudate. In putamen rostral to the level of globus pallidus, loss of PARV+ interneurons was more gradual, not dropping off to less than 20% of control until grade 2. Loss of PARV+ interneurons was even more gradual in motor putamen at globus pallidus levels, with no loss at grade 1, and steady grade-wise decline thereafter. A large decrease in striatal PARV+ interneurons, thus, occurs in HD with advancing disease grade, with regional variation in the loss per grade. Given the findings of animal studies and the grade-wise loss of PARV+ striatal interneurons in motor striatum in parallel with the grade-wise appearance and worsening of dystonia, our results raise the possibility that loss of PARV+ striatal interneurons is a contributor to dystonia in HD.
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PMID:Striatal parvalbuminergic neurons are lost in Huntington's disease: implications for dystonia. 2401 43