UMR Inserm U1253, iBrain, Université de Tours, UFR de Médecine, 10 Boulevard Tonnellé, 37032, Tours Cedex 01, France.
INSERM CIC 1415, University Hospital, Tours, France.
Mol Imaging Biol. 2020 Apr;22(2):348-357. doi: 10.1007/s11307-019-01400-y.
The nicotinic acetylcholine alpha-7 receptors (α7R) are involved in a number of neuropsychiatric and neurodegenerative brain disorders such as Parkinson's disease (PD). However, their specific pathophysiologic roles are still unclear. In this context, we studied the evolution of these receptors in vivo by positron emission tomography (PET) imaging using the recently developed tracer 3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-[F]fluorodibenzo[b,d]thiophene-5,5-dioxide) in a rat model mimicking early stages of PD.
PET imaging of α7R was performed at 3, 7, and 14 days following a partial striatal unilateral lesion with 6-hydroxydopamine in adult rats. After the last imaging experiments, the status of nigro-striatal dopamine neurons as well as different markers of neuroinflammation was evaluated on brain sections by autoradiographic and immunofluorescent experiments.
We showed an early and transitory rise in α7R expression in the lesioned striatum and substantia nigra, followed by over-expression of several gliosis activation markers in these regions of interest.
These findings support a longitudinally follow-up of α7R in animal models of PD and highlight the requirement to use a potential neuroprotective approach through α7R ligands at the early stages of PD.
烟碱型乙酰胆碱 α-7 受体 (α7R) 参与多种神经精神和神经退行性脑疾病，如帕金森病 (PD)。然而，其特定的病理生理作用仍不清楚。在这方面，我们通过正电子发射断层扫描 (PET) 成像，使用最近开发的示踪剂 3-(1,4-二氮杂双环[3.2.2]壬烷-4-基)-6-[F]氟二苯并[b,d]噻吩-5,5-二氧化物)，在模拟 PD 早期阶段的大鼠模型中研究了这些受体的体内演变。
在成年大鼠单侧纹状体用 6-羟多巴胺部分损伤后 3、7 和 14 天进行 α7R 的 PET 成像。在最后一次成像实验后，通过放射自显影和免疫荧光实验在脑切片上评估黑质纹状体多巴胺神经元的状态以及神经炎症的不同标志物。
我们显示在损伤的纹状体和黑质中 α7R 表达的早期和短暂增加，随后这些感兴趣区域中几种神经胶质激活标志物的过度表达。
这些发现支持在 PD 动物模型中对 α7R 进行纵向随访，并强调需要在 PD 的早期阶段使用 α7R 配体通过潜在的神经保护方法。
