Abnormal striatal and thalamic dopamine neurotransmission Genotype-related features of dystonia

被引：85

作者：

Carbon, M. ^{[1
,2
,3
]}

Niethammer, M. ^{[1
]}

Peng, S. ^{[1
]}

Raymond, D. ^{[4
]}

Dhawan, V. ^{[1
,2
,3
]}

Chaly, T. ^{[1
,2
,3
]}

Ma, Y. ^{[1
,2
,3
]}

Bressman, S. ^{[4
]}

Eidelberg, D. ^{[1
,2
,3
]}

机构：

[1] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Ctr Neurosci, Manhasset, NY 11030 USA

[2] N Shore Univ Hosp, Dept Neurol, New York, NY USA

[3] N Shore Univ Hosp, Dept Med, New York, NY USA

[4] Beth Israel Deaconess Med Ctr, Mirken Dept Neurol, New York, NY 10003 USA

来源：

NEUROLOGY | 2009年 / 72卷 / 24期

关键词：

PRIMARY TORSION DYSTONIA; DYT1; DYSTONIA; MOVEMENT-DISORDERS; NEURONAL-ACTIVITY; MOTOR DEFICITS; BASAL GANGLIA; MOUSE MODEL; BRAIN; MICE; HYPERACTIVITY;

D O I：

10.1212/WNL.0b013e3181aa538f

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 [C-11] 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 < 0.001). The changes were greater in DYT6 relative to DYT1 carriers (-38.0 +/- 3.0% vs -15.0 +/- 3.0%, p < 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 (R) 2009;72:2097-2103

引用

页码：2097 / 2103

页数：7