Decreased pallidal vesicular monoamine transporter type 2 availability in Parkinson's disease: The contribution of the nigropallidal pathway

Cho, Sang Soo; Christopher, Leigh; Koshimori, Yuko; Li, Crystal; Lang, Anthony E.; Houle, Sylvain; Strafella, Antonio P.

doi:10.1016/j.nbd.2018.11.022

Cited by 12 publications

(9 citation statements)

References 51 publications

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“…The observed reduction of VMAT2 density as measured by [ 11 C]DTBZ in our PD patient sample in the putamen, caudate, substantia nigra, and globus pallidus relative to controls is consistent with previous neuroimaging studies of VMAT2 (7,(37)(38)(39)(40). This reinforces the notion that [ 11 C]DTBZ PET imaging holds the potential to effectively differentiate PD patients from controls (41,42).…”

Section: Discussionsupporting

confidence: 90%

“…Another limitation is that patients were assessed on several clinical measures while "ON" dopamine replacement therapy and they were "OFF" medication during the PET scan. In turn, the relationship between motor severity and dopaminergic degeneration within the basal ganglia may not be fully representative even though VMAT2 was shown to be less prone to medication in uences (37). Although we showed a relationship between nigrostriatal innervation and motor score in PD patients without RBD, investigating motor features while "ON" and "OFF" medication and changes with VMAT2 levels may provide more insight about the true relationship observed between PD with and without RBD and motor severity in relation to the left caudate VMAT2 availability.…”

Section: Discussionmentioning

confidence: 99%

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VMAT2 Availability in Parkinson’s Disease with REM Sleep Behaviour Disorder

Valli¹,

Cho²,

Uribe³

et al. 2021

Preprint

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REM sleep behaviour disorder (RBD) is an early sleep disturbance symptom of Parkinson’s disease (PD) thought to be caused by the disruption of normal basal ganglia function due to neurodegeneration. To further elucidate the neuropathological contribution of RBD in PD, we aimed to characterize the role of vesicular monoamine transporter 2 (VMAT2), an index of nigrostriatal dopamine innervation, in PD patients with RBD (PD-RBD+). We identified 15 PD-RBD+, 15 PD patients without RBD (PD-RBD–) and 15 age matched healthy controls (HC) who underwent [11C]DTBZ PET imaging. This technique measures VMAT2 availability within striatal regions of interest (ROI). Mixed effect model was used to compare the radioligand binding of VMAT2 between the three groups for each striatal ROI, while co-varying for sex, cognitive function and depression scores. Multiple regressions were also computed to predict clinical measures from group condition and VMAT2 binding within all ROIs explored. Significant level was set at p < 0.05 (Bonferroni corrected). We observed significant main effect of group condition on VMAT2 availability within the caudate, putamen, ventral striatum, globus pallidus, substantia nigra, and subthalamus. Specifically, we observed that both PD-RBD + and PD-RBD– group had lower VMAT2 availability compared to HC. PD-RBD– showed a negative relationship between motor severity and VMAT2 availability within the left caudate. This relationship was not found in the PD-RBD + group. Our findings reveal that both PD patient subgroups had reduced VMAT2 levels relative to HC—which reflects denervation within the nigrostriatal pathway. No significant interactions were detected between radioligand binding and clinical scores in PD-RBD+. Taken together, we found limited evidence that VMAT2 may contribute differently in PD-RBD + relative to PD-RBD–. Future studies are encouraged to explore other underlying neural chemistry mechanisms contributing to RBD in PD patients.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

VMAT2 Availability in Parkinson’s Disease with REM Sleep Behaviour Disorder

Valli¹,

Cho²,

Uribe³

et al. 2021

Preprint

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“…A decrease in VMAT2 (and glucose metabolism) was observed in the lateral globus pallidus after STN DBS. Decreased pallidal VMAT2 in PD was shown in a recent study, which may explain why this region is affected by STN DBS [29]. The ventral striatum shows less of a change than the other striatal sub-regions, but does show a 9% decrease.…”

Section: Discussionmentioning

confidence: 71%

Effect of STN DBS on vesicular monoamine transporter 2 and glucose metabolism in Parkinson's disease

Smith

Mills

Pontone

et al. 2019

Parkinsonism & Related Disorders

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Introduction: Deep brain stimulation (DBS) is an established treatment for Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of subthalamic nucleus (STN) DBS in PD on the dopamine system and neural circuitry, employing high-resolution

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“…Decreased SLC18A2, STMN2, and SV2C expressions were found in the brain tissues from patients with PD. All three genes were considered a potential contributor to the pathogenesis of PD by regulating the synaptic vesicle function and then dopamine neuron function (Dunn et al, 2017;Lohr et al, 2017;Cho et al, 2019;Wang et al, 2019). The activated DC and gamma delta T cells may also have some potential links with the pathology of PD, which remains to be further explored.…”

Section: Discussionmentioning

confidence: 99%

Significant Difference of Immune Cell Fractions and Their Correlations With Differential Expression Genes in Parkinson’s Disease

Huang

Liu

et al. 2021

Front. Aging Neurosci.

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Parkinson’s disease (PD) is the second most neurodegenerative disease in the world. T cell infiltration in the central nervous system (CNS) has provided insights that the peripheral immune cells participate in the pathogenesis of PD. However, the association between the peripheral immune system and CNS remains to be elucidated. In this study, we analyzed incorporative substantia nigra (SN) expression data and blood expression data using the CIBERSORT to obtain the 22 immune cell fractions and then explored the molecular function to identify the potential key immune cell types and genes of PD. We observed that the proportions of naïve CD4 T cells, gamma delta T cells, resting natural killer (NK) cells, neutrophils in the blood, and regulatory T cells (Tregs) in the SN were significantly different between patients with PD and healthy controls (HCs). We identified p53-induced death domain protein 1 (PIDD1) as the hub gene of a PD-related module. The enrichment score of the neuron-specific gene set was significantly different between PD and HC, and genes in the neuron-related module were enriched in the biological process about mitochondria and synapses. These results suggested that the fractions of naïve CD4 T cells, gamma delta T cells, resting NK cells, and neutrophils may be used as a combined diagnostic marker in the blood, and Tregs in SN may be a potential therapeutic design target for PD.

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Decreased pallidal vesicular monoamine transporter type 2 availability in Parkinson's disease: The contribution of the nigropallidal pathway

Cited by 12 publications

References 51 publications

VMAT2 Availability in Parkinson’s Disease with REM Sleep Behaviour Disorder

VMAT2 Availability in Parkinson’s Disease with REM Sleep Behaviour Disorder

Effect of STN DBS on vesicular monoamine transporter 2 and glucose metabolism in Parkinson's disease

Significant Difference of Immune Cell Fractions and Their Correlations With Differential Expression Genes in Parkinson’s Disease

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