Imaging synaptic density in the living human brain
Imaging synaptic density in the living human brain
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DOI：
10.1126/scitranslmed.aaf6667
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发表时间：
2016-07-20
影响因子：
17.1
通讯作者：
Carson, Richard E.
中科院分区：
文献类型：
--
作者：
Finnema, Sjoerd J.;Nabulsi, Nabeel B.;Carson, Richard E.
化学突触是中枢神经系统中主要的神经元-神经元接触。神经元的突触前终扣含有数百个充满神经递质的囊泡，神经递质是一种可扩散的信号化学物质。突触数量的变化与许多脑部疾病有关，包括阿尔茨海默病和癫痫。然而，目前所有测量人类突触密度的方法都需要尸检或手术切除的脑组织。我们报告使用突触囊泡糖蛋白2A（SV 2A）放射性配体[C-11]UCB-J结合正电子发射断层扫描（PET）来量化活体人脑中的突触密度。在狒狒中的验证研究证实，SV 2A是突触体蛋白的替代突触密度标记物。首次人体PET研究表明，[C-11]UCB-J具有优异的成像特性。最后，我们证实了SV 2A的PET成像对颞叶癫痫患者的突触丢失敏感。因此，[C-11]UCB-J PET成像是体内定量突触密度的一种有前途的方法，在神经和精神疾病的诊断和治疗监测中具有几种潜在的应用。
Chemical synapses are the predominant neuron-to-neuron contact in the central nervous system. Presynaptic boutons of neurons contain hundreds of vesicles filled with neurotransmitters, the diffusible signaling chemicals. Changes in the number of synapses are associated with numerous brain disorders, including Alzheimer's disease and epilepsy. However, all current approaches for measuring synaptic density in humans require brain tissue from autopsy or surgical resection. We report the use of the synaptic vesicle glycoprotein 2A (SV2A) radioligand [C-11]UCB-J combined with positron emission tomography (PET) to quantify synaptic density in the living human brain. Validation studies in a baboon confirmed that SV2A is an alternative synaptic density marker to synaptophysin. First-in-human PET studies demonstrated that [C-11]UCB-J had excellent imaging properties. Finally, we confirmed that PET imaging of SV2A was sensitive to synaptic loss in patients with temporal lobe epilepsy. Thus, [C-11]UCB-J PET imaging is a promising approach for in vivo quantification of synaptic density with several potential applications in diagnosis and therapeutic monitoring of neurological and psychiatric disorders.