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Lookup NU author(s): Professor David BrooksORCiD
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Sage Publications Ltd, 2021.
For re-use rights please refer to the publisher's terms and conditions.
The number of functionally active synapses provides a measure of neural integrity, with reductions observed in neurodegenerative disorders. [11C]UCB-J binds to synaptic vesicle 2A (SV2A) transmembrane protein located in secretory vesicles. We aimed to assess [11C]UCB-J PET as an in vivo biomarker of regional cerebral synaptic SV2A density in rat lesion models of neurodegeneration. Healthy anesthetized rats had [11C]UCB-J PET and arterial blood sampling. We compared different models describing [11C]UCB-J brain uptake kinetics to determine its regional distribution. Blocking studies.were performed with levetiracetam (LEV), an antiepileptic SV2A antagonist. Tracer binding was measured in rodent unilateral acute lesion models of Parkinsonism and Huntington’s disease, induced with 6-hydroxydopamine (6-OHDA) and quinolinic acid (QA), respectively. [3H]UCB-J autoradiography was performed in postmortem tissue. Rat brain showed high and fast [11C]UCB-J uptake and washout with up to 80% blockade by LEV. [11C]UCB-J PET showed a 6.2%,decrease in ipsilateral striatal SV2A binding after 6- OHDA and 39.3% and 55.1% decreases after moderate and high dose QA confirmed by autoradiography. In conclusion, [11C]UCB-J PET provides a good in vivo marker of synaptic SV2A density which can potentially be followed longitudinally along with synaptic responses to putative neuroprotective agents in models of neurodegeneration.
Author(s): Thomsen MB, Jacobsen J, Lillethorup TP, Schacht AC, Simonsen M, Romero-Ramos M, Brooks DJ, Landau AM
Publication type: Article
Publication status: Published
Journal: Journal of Cerebral Blood Flow and Metabolism
Year: 2021
Volume: 41
Issue: 4
Pages: 819-830
Print publication date: 01/04/2021
Online publication date: 14/06/2020
Acceptance date: 06/05/2020
Date deposited: 06/05/2020
ISSN (print): 0271-678X
ISSN (electronic): 1559-7016
Publisher: Sage Publications Ltd
URL: https://doi.org/10.1177/0271678X20931140
DOI: 10.1177/0271678X20931140
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