Primate models of dystonia

Guehl, Dominique; Cuny, Emmanuel; Ghorayeb, Imad; Michelet, Thomas; Bioulac, Bernard; Burbaud, Pierre

doi:10.1016/j.pneurobio.2008.10.003

Cited by 49 publications

(40 citation statements)

References 134 publications

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“…Dystonic movements have been reported following a variety of manipulations in different experimental animals including non-human primates [7], cats, and rodents [8, 9]. Many of these studies include careful descriptions of abnormal movements, often with accompanying video demonstrations that fulfill currently accepted clinical criteria for “dystonia” [8, 9].…”

Section: Motor Pathways Involved In Dystonia (Ha Jinnah Yoland Smimentioning

confidence: 99%

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia

et al. 2016

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A role for the cerebellum in causing ataxia, a disorder characterized by uncoordinated movement, is widely accepted. Recent work has suggested that alterations in activity, connectivity, and structure of the cerebellum are also associated with dystonia, a neurological disorder characterized by abnormal and sustained muscle contractions often leading to abnormal maintained postures. In this manuscript, the authors discuss their views on how the cerebellum may play a role in dystonia. The following topics are discussed: The relationships between neuronal/network dysfunctions and motor abnormalities in rodent models of dystonia.Data about brain structure, cerebellar metabolism, cerebellar connections, and noninvasive cerebellar stimulation that support (or not) a role for the cerebellum in human dystonia.Connections between the cerebellum and motor cortical and sub-cortical structures that could support a role for the cerebellum in dystonia. Overall points of consensus include: Neuronal dysfunction originating in the cerebellum can drive dystonic movements in rodent model systems.Imaging and neurophysiological studies in humans suggest that the cerebellum plays a role in the pathophysiology of dystonia, but do not provide conclusive evidence that the cerebellum is the primary or sole neuroanatomical site of origin.

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Section: Motor Pathways Involved In Dystonia (Ha Jinnah Yoland Smimentioning

confidence: 99%

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia

et al. 2016

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“…Dystonic like posturing can be induced in primates by lesioning or pharmacologic manipulation of the midbrain and basal ganglia [53]. These models are however not informative as to whether and how the cerebellum may contribute to human dystonia.…”

Section: Physiological Correlates Of Primary Dystoniamentioning

confidence: 99%

Physiologic Changes Associated with Cerebellar Dystonia

Shakkottai

2014

Cerebellum

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Dystonia is a neurologic disorder characterized by sustained involuntary muscle contractions. Lesions responsible for unilateral secondary dystonia are confined to the putamen, caudate, globus pallidus and thalamus. Dysfunction of these structures is suspected to play a role in both primary and secondary dystonia. Recent evidence has suggested that the cerebellum may play a role in the pathophysiology of dystonia. The role of the cerebellum in ataxia, a disorder of motor incoordination is well established. How may the cerebellum contribute to two apparently very different movement disorders? This review will discuss the idea of whether in some cases, ataxia and dystonia lie in the same clinical spectrum, and whether graded perturbations in cerebellar function may explain a similar causative role for the cerebellum in these two different motor disorders. The review also proposes a model for cerebellar dystonia based on the available animal models of this disorder.

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“…12 Similar inconsistencies have also been found in non-DYT1 experimental models of dystonia. [13][14][15][16] In the current study, we sought to identify changes in D 2 receptor availability linked to the presence of clinical manifestations in a cohort of DYT1 and DYT6 gene carriers. We expanded upon our earlier [ 11 C] raclopride (RAC) PET investigation of nonmanifesting DYT1 carriers 5 to determine whether greater reductions in striatal D 2 receptor binding are present in manifesting DYT1 carriers, and whether comparable changes occur in manifesting and nonmanifesting carriers of the DYT6 haplotype.…”

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Abnormal striatal and thalamic dopamine neurotransmission

Carbon

Niethammer²,

Peng³

et al. 2009

Neurology

118

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Objective: To determine whether changes in D 2 receptor availability are present in carriers of genetic mutations for primary dystonia. Methods:Manifesting and nonmanifesting carriers of the DYT1 and DYT6 dystonia mutations were scanned with [11 C] raclopride (RAC) and PET. Measures of D 2 receptor availability in the caudate nucleus and putamen were determined using an automated region-of-interest approach.Values from mutation carriers and healthy controls were compared using analysis of variance to assess the effects of genotype and phenotype. Additionally, voxel-based whole brain searches were conducted to detect group differences in extrastriatal regions.Results: Significant reductions in caudate and putamen D 2 receptor availability were evident in both groups of mutation carriers relative to healthy controls (p Ͻ 0.001). The changes were greater in DYT6 relative to DYT1 carriers (Ϫ38.0 Ϯ 3.0% vs Ϫ15.0 Ϯ 3.0%, p Ͻ 0.001). By contrast, there was no significant difference between manifesting and nonmanifesting carriers of either genotype. Voxel-based analysis confirmed these findings and additionally revealed reduced RAC binding in the ventrolateral thalamus of both groups of mutation carriers. As in the striatum, the thalamic binding reductions were more pronounced in DYT6 carriers and were not influenced by the presence of clinical manifestations. Conclusions:Reduced D 2 receptor availability in carriers of dystonia genes is compatible with dysfunction or loss of D 2 -bearing neurons, increased synaptic dopamine levels, or both. These changes, which may be present to different degrees in the DYT1 and DYT6 genotypes, are likely to represent susceptibility factors for the development of clinical manifestations in mutation carriers. Neurology GLOSSARY ANOVA ϭ analysis of variance; BFM ϭ Burke-Fahn-Marsden; CN ϭ caudate nucleus; FWE ϭ family-wise error rate; GPe ϭ external pallidum; GPi ϭ interal pallidum; RAC ϭ raclopride; ROI ϭ region of interest; SOR ϭ striato-occipital ratio; THX ϭ trihexyphenidyl; VL ϭ ventrolateral tier nuclei.Multiple lines of evidence support the role of altered striatal DA neurotransmission in primary dystonia. 1,2 Nonetheless, imaging studies have revealed only minimal reductions in striatal D 2 receptor binding in patients with idiopathic dystonia 3,4 and in nonmanifesting carriers of the DYT1 dystonia mutation.5 Indeed, similar reductions have been described in DYT1 dystonia patients at postmortem.1 It is not known whether similar abnormalities are also present in primary dystonia associated with other genetic mutations.Experimental models of dystonia have yielded varied results with regard to the striatal DA dynamics. Increased striatal DA turnover was found in a transgenic murine DYT1 model regardless of behavioral phenotype. 6,7 However, in this model, striatal DA levels were reduced

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Primate models of dystonia

Cited by 49 publications

References 134 publications

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia

Physiologic Changes Associated with Cerebellar Dystonia

Abnormal striatal and thalamic dopamine neurotransmission

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