Department of Radiology and Biomedical Imaging, Yale PET Center, Yale School of Medicine, New Haven, CT, USA.
Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
Eur J Nucl Med Mol Imaging. 2022 Sep;49(11):3679-3691. doi: 10.1007/s00259-022-05825-6. Epub 2022 May 28.
Exploring synaptic density changes during brain growth is crucial to understanding brain development. Previous studies in nonhuman primates report a rapid increase in synapse number between the late gestational period and the early neonatal period, such that synaptic density approaches adult levels by birth. Prenatal synaptic development may have an enduring impact on postnatal brain development, but precisely how synaptic density changes in utero are unknown because current methods to quantify synaptic density are invasive and require post-mortem brain tissue.
We used synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) radioligands [C]UCB-J and [F]Syn-VesT-1 to conduct the first assessment of synaptic density in the developing fetal brain in gravid rhesus monkeys. Eight pregnant monkeys were scanned twice during the third trimester at two imaging sites. Fetal post-mortem samples were collected near term in a subset of subjects to quantify SV2A density by Western blot.
Image-derived fetal brain SV2A measures increased during the third trimester. SV2A concentrations were greater in subcortical regions than in cortical regions at both gestational ages. Near term, SV2A density was higher in primary motor and visual areas than respective associative regions. Post-mortem quantification of SV2A density was significantly correlated with regional SV2A PET measures.
While further study is needed to determine the exact relationship of SV2A and synaptic density, the imaging paradigm developed in the current study allows for the effective in vivo study of SV2A development in the fetal brain.
探索大脑生长过程中突触密度的变化对于理解大脑发育至关重要。之前在非人类灵长类动物中的研究报告表明，突触数量在妊娠晚期到新生儿早期之间迅速增加，以至于突触密度在出生时接近成人水平。产前的突触发育可能对出生后的大脑发育产生持久的影响，但由于目前用于量化突触密度的方法具有侵入性，并且需要死后脑组织，因此尚不清楚子宫内突触密度是如何变化的。
我们使用突触小泡糖蛋白 2A（SV2A）正电子发射断层扫描（PET）放射性配体 [C]UCB-J 和 [F]Syn-VesT-1，首次评估了妊娠恒河猴胎儿大脑中的突触密度。在两个成像部位，八只妊娠猴子在妊娠晚期进行了两次扫描。在一组亚组中，胎儿死后样本在接近足月时收集，通过 Western blot 定量 SV2A 密度。
图像衍生的胎儿脑 SV2A 测量值在妊娠晚期增加。在两个胎龄时，皮质下区域的 SV2A 浓度均高于皮质区域。接近足月时，初级运动和视觉区域的 SV2A 密度高于相应的联合区域。SV2A 密度的死后定量与区域 SV2A PET 测量值显著相关。
虽然需要进一步研究来确定 SV2A 与突触密度的确切关系，但目前研究中开发的成像方案允许有效地在体内研究胎儿大脑中的 SV2A 发育。
