Functional anatomy of the basal ganglia in X‐linked recessive dystonia‐parkinsonism

Goto, Satoshi; Lee, Lillian V.; Muñoz, Edwin L.; Tooyama, Ikuo; Tamiya, Gen; Makino, Satoshi; Ando, Satoshi; Dantes, Marita; Yamada, Kazumichi; Matsumoto, Sadayuki; Shimazu, Hideki; Kuratsu, Jun Ichi; Hirano, Atsushi; Kaji, Ryuji

doi:10.1002/ana.20513

Cited by 172 publications

(178 citation statements)

References 47 publications

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“…Differential degeneration of striosomes has been found in a postmortem analysis of the brains of DYT3 patients (33). Thus an important question to pursue is whether some dystonias are linked to a disproportionate loss of normal activity in the striosome compartment, and whether their hypokinetic or hyperkinetic character depends on the associated dopaminergic activities in the matrix compartment.…”

Section: Discussionmentioning

confidence: 99%

Differential involvement of striosome and matrix dopamine systems in a transgenic model of dopa-responsive dystonia

Sato

Sumi‐Ichinose

Kaji

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Dopa-responsive dystonia (DRD) is a hereditary dystonia character-ized by a childhood onset of fixed dystonic posture with a dramatic and sustained response to relatively low doses of levodopa. DRD is thought to result from striatal dopamine deficiency due to a reduced synthesis and activity of tyrosine hydroxylase (TH), the synthetic enzyme for dopamine. The mechanisms underlying the genesis of dystonia in DRD present a challenge to models of basal ganglia movement control, given that striatal dopamine deficiency is the hallmark of Parkinson's disease. We report here behavioral and anatomical observations on a transgenic mouse model for DRD in which the gene for 6-pyruvoyl-tetrahydropterin synthase is targeted to render selective dysfunction of TH synthesis in the striatum. Mutant mice exhibited motor deficits phenotypically resembling symptoms of human DRD and manifested a major depletion of TH labeling in the striatum, with a marked posterior-to-anterior gradient resulting in near total loss caudally. Strikingly, within the regions of remaining TH staining in the striatum, there was a greater loss of TH labeling in striosomes than in the surrounding matrix. The predominant loss of TH expression in striosomes occurred during the early postnatal period, when motor symptoms first appeared. We suggest that the differential striosome-matrix pattern of dopamine loss could be a key to identifying the mechanisms underlying the genesis of dystonia in DRD.basal ganglia ͉ movement disorders ͉ Parkinson's disease ͉ striatum

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Section: Discussionmentioning

confidence: 99%

Differential involvement of striosome and matrix dopamine systems in a transgenic model of dopa-responsive dystonia

Sato

Sumi‐Ichinose

Kaji

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Goto et al [13] identified loss of calcineurinexpressing neurons with accompanying gliosis in the striosome compartment in the early stage of XDP. They proposed that selective neuronal death within the striatum might result in an imbalance in activity between the striosomal and matrix-based pathways.…”

Section: Discussionmentioning

confidence: 99%

Differential Response of Dystonia and Parkinsonism following Globus Pallidus Internus Deep Brain Stimulation in X-Linked Dystonia-Parkinsonism (Lubag)

Oyama¹,

Fernández²,

Foote³

et al. 2010

Stereotact Funct Neurosurg

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Background: X-linked dystonia-parkinsonism (XDP; DYT3; Lubag) is an adult-onset hereditary progressive dystonia/parkinsonism which is typically minimally responsive to pharmacological treatment. Case Report: We report a 63- year-old man with a diagnosis of XDP who underwent bilateral globus pallidus internus deep brain stimulator (GPi-DBS) placement. His course initially began with right hand tremor and dystonia at age 57 and progressed to also include bradykinesia and rigidity. The patient tolerated the procedure without significant complications. GPi-DBS improved his right hand dystonia, but did not significantly improve his parkinsonism. Conclusion: DBS may be a therapeutic option for select cases of XDP, but its specificindications must be carefully discussed, as the available cases have had mixed responses. Whether other targets may be more effective is not known.

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“…The dysfunction of striatal matrix neurons is especially severe for the indirect pathway neurons of the striatum, which in the sensorimotor striatum receive powerful inputs from the motor cortex (4)(5)(6). In different models of parkinsonian states, the gradients and compartmental expression of dopaminergic deficits vary (7)(8)(9), but it seems likely that dysfunctional dopaminergic modulation of corticostriatal motor pathways leading through the matrix compartment is a major contributor to the motor symptoms of Parkinson's disease, and that in a range of movement disorders, compartmentally selective striatal dysfunction is present (10)(11)(12)(13)(14)(15)(16)(17).…”

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confidence: 99%

Dysregulation of CalDAG-GEFI and CalDAG-GEFII predicts the severity of motor side-effects induced by anti-parkinsonian therapy

Crittenden

Cantuti-Castelvetri²,

Saka³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Voluntary movement difficulties in Parkinson's disease are initially relieved by L-DOPA therapy, but with disease progression, the repeated L-DOPA treatments can produce debilitating motor abnormalities known as L-DOPA-induced dyskinesias. We show here that 2 striatum-enriched regulators of the Ras/Rap/ERK MAP kinase signal transduction cascade, matrix-enriched CalDAG-GEFI and striosome-enriched CalDAG-GEFII (also known as RasGRP), are strongly and inversely dysregulated in proportion to the severity of abnormal movements induced by L-DOPA in a rat model of parkinsonism. In the dopamine-depleted striatum, the L-DOPA treatments produce down-regulation of CalDAG-GEFI and upregulation of CalDAG-GEFII mRNAs and proteins, and quantification of the mRNA levels shows that these changes are closely correlated with the severity of the dyskinesias. As these CalDAGGEFs control ERK cascades, which are implicated in L-DOPA-induced dyskinesias, and have differential compartmental expression patterns in the striatum, we suggest that they may be key molecules involved in the expression of the dyskinesias. They thus represent promising new therapeutic targets for limiting the motor complications induced by L-DOPA therapy.dyskinesia ͉ ERK ͉ L-DOPA ͉ Parkinson's disease ͉ striatum

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Functional anatomy of the basal ganglia in X‐linked recessive dystonia‐parkinsonism

Cited by 172 publications

References 47 publications

Differential involvement of striosome and matrix dopamine systems in a transgenic model of dopa-responsive dystonia

Differential involvement of striosome and matrix dopamine systems in a transgenic model of dopa-responsive dystonia

Differential Response of Dystonia and Parkinsonism following Globus Pallidus Internus Deep Brain Stimulation in X-Linked Dystonia-Parkinsonism (Lubag)

Dysregulation of CalDAG-GEFI and CalDAG-GEFII predicts the severity of motor side-effects induced by anti-parkinsonian therapy

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