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Dopaminergic Positron Emission Tomography Imaging in the Alpha-Synuclein Preformed Fibril Model Reveals Similarities to Early Parkinson's Disease.

التفاصيل البيبلوغرافية
العنوان: Dopaminergic Positron Emission Tomography Imaging in the Alpha-Synuclein Preformed Fibril Model Reveals Similarities to Early Parkinson's Disease.
المؤلفون: Sossi V; Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada., Patterson JR; Department of Translational Neuroscience, Michigan State University, Grand Rapids, Michigan, USA., McCormick S; Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada., Kemp CJ; Department of Translational Neuroscience, Michigan State University, Grand Rapids, Michigan, USA., Miller KM; Department of Translational Neuroscience, Michigan State University, Grand Rapids, Michigan, USA., Stoll AC; Department of Translational Neuroscience, Michigan State University, Grand Rapids, Michigan, USA., Kuhn N; Department of Translational Neuroscience, Michigan State University, Grand Rapids, Michigan, USA., Kubik M; Department of Translational Neuroscience, Michigan State University, Grand Rapids, Michigan, USA., Kochmanski J; Department of Translational Neuroscience, Michigan State University, Grand Rapids, Michigan, USA., Luk KC; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Sortwell CE; Department of Translational Neuroscience, Michigan State University, Grand Rapids, Michigan, USA.
المصدر: Movement disorders : official journal of the Movement Disorder Society [Mov Disord] 2022 Aug; Vol. 37 (8), pp. 1739-1748. Date of Electronic Publication: 2022 May 07.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8610688 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-8257 (Electronic) Linking ISSN: 08853185 NLM ISO Abbreviation: Mov Disord Subsets: MEDLINE
أسماء مطبوعة: Publication: <2001->: New York, NY : Wiley-Liss
Original Publication: [New York, N.Y.] : Raven Press, [c1986-
مواضيع طبية MeSH: Parkinson Disease*/diagnostic imaging , Parkinson Disease*/metabolism , alpha-Synuclein*/metabolism, Animals ; Corpus Striatum/metabolism ; Dopamine/metabolism ; Dopaminergic Neurons/metabolism ; Humans ; Positron-Emission Tomography ; Rats
مستخلص: Background: Positron emission tomography (PET) imaging in early Parkinson's disease (PD) subjects reveals that increased dopamine (DA) turnover and reduced dopamine transporter (DAT) density precede decreases in DA synthesis and storage. The rat α-synuclein preformed fibril (α-syn PFF) model provides a platform to investigate DA dynamics during multiple stages of α-syn inclusion-triggered nigrostriatal degeneration.
Objectives: We investigated multiple aspects of in vivo dopaminergic deficits longitudinally and similarities to human PD using translational PET imaging readouts.
Methods: Longitudinal imaging was performed every 2 months in PFF and control rats for 7 months. [ 18 F]-Fluoro-3,4-dihydroxyphenyl-L-alanine (FDOPA) imaging was performed to investigate DA synthesis and storage (K occ ) and DA turnover, estimated by its inverse, the effective distribution volume ratio (EDVR). 11 C-Methylphenidate (MP) was used to estimate DAT density (BP ND ).
Results: Early DA turnover increases and DAT binding decreases were observed in the ipsilateral striatum of PFF rats, progressing longitudinally. EDVR decreased 26%, 38%, and 47%, and BP ND decreased 36%, 50%, and 65% at the 2-, 4-, and 6-month time points, respectively, compared to ipsilateral control striatum. In contrast, deficits in DA synthesis and storage were not observed in the ipsilateral striatum of PFF rats compared to control injections and were relatively preserved up to 6 months (K occ decreased 20% at 6 months).
Conclusions: The relative preservation of DA synthesis and storage compared to robust progressive deficits in DAT density and increases in DA turnover in the rat α-syn PFF model display remarkable face validity to dopaminergic alterations in human PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
(© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
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معلومات مُعتمدة: R21 NS099416 United States NS NINDS NIH HHS; R33 NS099416 United States NS NINDS NIH HHS; T32 GM142521 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: PET imaging; alpha-synuclein; nigrostriatal system; rodent model; synucleinopathy
المشرفين على المادة: 0 (alpha-Synuclein)
VTD58H1Z2X (Dopamine)
تواريخ الأحداث: Date Created: 20220507 Date Completed: 20220819 Latest Revision: 20231114
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9391270
DOI: 10.1002/mds.29051
PMID: 35524682
قاعدة البيانات: MEDLINE
الوصف
تدمد:1531-8257
DOI:10.1002/mds.29051