Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Huntington's disease (HD) is a fatal genetic neurodegenerative disorder. It has mainly been considered a movement disorder with cognitive symptoms and these features have been associated with pathology of the striatum and cerebral cortex. Importantly, individuals with the mutant huntingtin gene suffer from a spectrum of non-motor features often decades before the motor disorder manifests. These symptoms and signs include a range of psychiatric symptoms, sleep problems and metabolic changes with weight loss particularly in later stages. A higher body mass index at diagnosis is associated with slower disease progression. The common psychiatric symptom of apathy progresses with the disease. The fact that non-motor features are present early in the disease and that they show an association to disease progression suggest that unravelling the underlying neurobiological mechanisms may uncover novel targets for early disease intervention and better symptomatic treatment. The hypothalamus and the limbic system are important brain regions that regulate emotion, social cognition, sleep and metabolism. A number of studies using neuroimaging, postmortem human tissue and genetic manipulation in animal models of the disease has collectively shown that the hypothalamus and the limbic system are affected in HD. These findings include the loss of neuropeptide-expressing neurons such as orexin (hypocretin), oxytocin, vasopressin, somatostatin and VIP, and increased levels of SIRT1 in distinct nuclei of the hypothalamus. This review provides a summary of the results obtained so far and highlights the potential importance of these changes for the understanding of non-motor features in HD.
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PMID:The Role of Hypothalamic Pathology for Non-Motor Features of Huntington's Disease. 3159 40