Illuminating basal ganglia and beyond in Parkinson's disease

Vaillancourt, David E.; Lehericy, Stéphane

doi:10.1002/mds.27483

Cited by 5 publications

(3 citation statements)

References 15 publications

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“…Parkinson's disease (PD) is a neurodegenerative disorder with pronounced progressive loss of dopamine-producing neurons in the substantia nigra compacta (SNc) ( Vaillancourt & Lehericy, 2018 ). The disease is primarily characterized by motor symptom, including resting tremors, bradykinesia, limb rigidity, and defects in gait and balance ( Obeso et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Dynamic Involvement of Striatal NG2-glia in L-DOPA Induced Dyskinesia in Parkinsonian Rats: Effects of Doxycycline

et al. 2023

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Levo-dihydroxyphenylalanine (L-DOPA) therapy for Parkinson's disease (PD) patients improves motor symptoms, but long-term treatment induces side effects such as abnormal involuntary movements (levodopa-induced dyskinesia – LID). Increasing evidence has linked LID with neuroinflammatory reaction in the striatum involving microglia and astrocytes. The nerve/glial antigen-2 cells (NG2-glia) are recognized as a glial cell whose function in the adult brain is poorly understood. Here, we used immunohistochemistry, confocal microscopy, and western blot to characterize the cellular distribution of NG2-glia in the dorsal striatum of unilaterally 6OHDA-lesioned rats presenting LID. The effect of doxycycline on NG2-glia cells was determined. Dopamine depletion revealed a minor density increase of NG2-glia in the dorsolateral striatum and an activated phenotype. LID development promotes a decrease in NG2-glia cell density and protein level, maintaining the cell-activated feature. Doxycycline antidyskinetic therapy restores the cells to the control density profile. These results indicated the cellular distribution of NG2-glia in the striatum, but the interaction between these cells and other glial types in this model was unanswered and therefore we carried out a double labeling of NG2 and OX-42 (microglia) and GFAP (astrocyte). In LID, there was a decrease in the possible NG2 and OX-42 positive cells interaction, with no effect in the astrocytes. Doxycycline treatment restored the control characteristic. The ability of NG2-glia to regulate their dynamics in response to PD and LID is the first indication of an active link between them. The results suggest that NG2 cells may play important roles other than serving as oligodendrocyte precursor cells. Summary Statement NG2-glia alters its dynamics in response to L-DOPA-induced dyskinesia. In these animals, striatal NG2-glia density was reduced with cells presenting activated phenotype while doxycycline antidyskinetic therapy promotes a return to NG2-glia cell density and protein to a not activated state.

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Section: Introductionmentioning

confidence: 99%

Dynamic Involvement of Striatal NG2-glia in L-DOPA Induced Dyskinesia in Parkinsonian Rats: Effects of Doxycycline

et al. 2023

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“…Nevertheless, although all these MRI techniques provide suitable markers for the nigral structure, they generally may not differentiate PD and other types of degenerative parkinsonism [ 116 ]. Further recent neuroimaging techniques, such as diffusion-tensor imaging and density imaging, might help clinicians to differentiate between these conditions but their unavailability on most scanners and the lack of normative databases challenge their use in clinical practice [ 300 , 301 ].…”

Section: Beyond Dat: Correlation With Other Potential Nigrostriatal Biomarkers In Pdmentioning

confidence: 99%

Dopamine Transporter Imaging, Current Status of a Potential Biomarker: A Comprehensive Review

Palermo

Giannoni

Bellini

et al. 2021

IJMS

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A major goal of current clinical research in Parkinson’s disease (PD) is the validation and standardization of biomarkers enabling early diagnosis, predicting outcomes, understanding PD pathophysiology, and demonstrating target engagement in clinical trials. Molecular imaging with specific dopamine-related tracers offers a practical indirect imaging biomarker of PD, serving as a powerful tool to assess the status of presynaptic nigrostriatal terminals. In this review we provide an update on the dopamine transporter (DAT) imaging in PD and translate recent findings to potentially valuable clinical practice applications. The role of DAT imaging as diagnostic, preclinical and predictive biomarker is discussed, especially in view of recent evidence questioning the incontrovertible correlation between striatal DAT binding and nigral cell or axon counts.

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“…Parkinson's disease (PD) is a neurodegenerative disorder, triggered by the progressive loss of dopamineproducing neurons in the substantia nigra compacta (SNc) region of the basal ganglia (Vaillancourt and Lehericy, 2018). The disease was considered mainly by motor symptomatology, including resting tremor, bradykinesia, limb rigidity, and defects in gait and balance (Obeso et al, 2018).…”

Section: Introduction (742 Words)mentioning

confidence: 99%

Neuron glial antigen 2 in the striatum of parkinsonian rats presenting L-DOPA induced dyskinesia

Nascimento¹,

Bortolanza²,

Del‐Bel³

2021

Preprint

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Nerve/glial antigen 2 glial cells (NG2-glia) are a uniformly distributed pool of cells in the central nervous system. In addition, to serve as oligodendrocytes progenitors, NG2-glia might also fulfil physiological roles, although such functions' mechanistic nature remains unclear. Here, we investigated NG2-glia expression in the striatum of 6-hydroxydopamine lesioned Wistar adult male rats presenting L-DOPA induced dyskinesia (LID). Immunoconfocal morphometry, immunohistochemistry, and western blot techniques were performed to label NG2-glia, astrocyte (GFAP), and microglia (OX-42) in the striatum. Our data revealed that the L-DOPA-induced dyskinesia produces a decrease of the NG2-glia density in the striatum, an area critical to Parkinson's disease pathophysiology L-DOPA induced dyskinesia instalment. NG2-glia presented a negative correlation with L-DOPA induced dyskinesia score opposing to GFAP and OX-42 immunopositive cells. The doxycycline antidyskinetic therapy induced a robust increment of NG2-glia restoring standards beforehand L-DOPA induced dyskinesia manifestation. The morphometric analysis identified a NG2 reactive phenotype

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Illuminating basal ganglia and beyond in Parkinson's disease

Cited by 5 publications

References 15 publications

Dynamic Involvement of Striatal NG2-glia in L-DOPA Induced Dyskinesia in Parkinsonian Rats: Effects of Doxycycline

Dynamic Involvement of Striatal NG2-glia in L-DOPA Induced Dyskinesia in Parkinsonian Rats: Effects of Doxycycline

Dopamine Transporter Imaging, Current Status of a Potential Biomarker: A Comprehensive Review

Neuron glial antigen 2 in the striatum of parkinsonian rats presenting L-DOPA induced dyskinesia

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