Adenosine A(2A) receptor availability in patients with early- and moderate-stage Parkinson's disease.
Adenosine A(2A) receptor availability in patients with early- and moderate-stage Parkinson's disease.
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DOI：
10.1007/s00415-022-11342-1
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发表时间：
2023-01
影响因子：
6
通讯作者：
Airas, Laura
中科院分区：
文献类型：
--
作者：
Waggan, Imran;Rissanen, Eero;Tuisku, Jouni;Joutsa, Juho;Helin, Semi;Parkkola, Riitta;Rinne, Juha O.;Airas, Laura
腺苷 2A (A2A) 受体与间接通路的纹状体苍白球中型多棘神经元中的多巴胺 D2 受体共定位。纹状体或苍白球中的 A2A 受体激活会降低 D2 信号传导。相反，A2A 受体拮抗作用可能有助于增强它。此外，之前的 PET 研究表明，患有运动障碍的晚期 PD 患者纹状体中 A2A 受体的可用性有所增加。然而，早期 PD 中纹状体 A2A 受体可用性的人体体内证据有限。本研究旨在调查无运动障碍的早期和中期 PD 患者纹状体和苍白球中 A2A 受体可用性的可能差异。对 9 名早期 PD 患者和 9 名无运动障碍的中期 PD 患者以及 6 名健康对照者进行了脑部 MRI 和 PET 使用 [11C]TMSX 放射性配体靶向 A2A 受体。计算分布体积比 (DVR) 以评估尾状核、壳核和苍白球中的特异性 [11C]TMSX 结合。与健康对照相比，早期 PD 患者双侧尾状核的 A2A 受体可用性 (DVR) 降低 (P = 0.02)。相反，与健康对照相比，中度 PD 患者的苍白球双侧 DVR 增加 (P = 0.03)。平均纹状体 DVR 增加与较高的运动症状严重程度相关 ( = 0.47，P = 0.02)。我们的结果表明，PD 病理生理学中 A2A 受体信号传导以及对多巴胺能药物的反应存在区域性和疾病阶段依赖性变化。在线版本包含可在 10.1007/s00415-022-11342-1 获取的补充材料。
Adenosine 2A (A2A) receptors co-localize with dopamine D2 receptors in striatopallidal medium spiny neurons of the indirect pathway. A2A receptor activation in the striatum or pallidum decreases D2 signaling. In contrast, A2A receptor antagonism may help potentiate it. Furthermore, previous PET studies have shown increased A2A receptor availability in striatum of late-stage PD patients with dyskinesia. However, human in vivo evidence for striatal A2A receptor availability in early-stage PD is limited. This study aimed to investigate possible differences in A2A receptor availability in the striatum and pallidum of early- and moderate-stage PD patients without dyskinesias. Brain MRI and PET with [11C]TMSX radioligand, targeting A2A receptors, was performed in 9 patients with early- and 9 with moderate-stage PD without dyskinesia and in 6 healthy controls. Distribution volume ratios (DVR) were calculated to assess specific [11C]TMSX binding in caudate, putamen and pallidum. A2A receptor availability (DVR) was decreased in the bilateral caudate of early-stage PD patients when compared with healthy controls (P = 0.02). Conversely, DVR was increased bilaterally in the pallidum of moderate-stage PD patients compared to healthy controls (P = 0.03). Increased mean striatal DVR correlated with higher motor symptom severity ( = 0.47, P = 0.02). Our results imply regional and disease stage-dependent changes in A2A receptor signaling in PD pathophysiology and in response to dopaminergic medication. The online version contains supplementary material available at 10.1007/s00415-022-11342-1.
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影响因子：
2.5
作者：
Hurley, MJ;Mash, DC;Jenner, P
通讯作者：
Jenner, P
影响因子：
8.6
作者：
Antonini, A;Schwarz, J;Leenders, KL
通讯作者：
Leenders, KL
DOI：
10.1073/pnas.1423088112
发表时间：
2015-06-23
影响因子：
11.1
作者：
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通讯作者：
Cunha, Rodrigo A.
影响因子：
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作者：
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影响因子：
4.7
作者：
Ko, Wai Kin D.;Camus, Sandrine M.;Bezard, Erwan
通讯作者：
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