Department of Neuroscience, Kavli Institute for Neuroscience, Yale School of Medicine, Yale University, New Haven, CT 6510, USA.
Gill Center for Biomolecular Science, Indiana University, Bloomington, IN 47405-2204, USA.
Int J Mol Sci. 2020 Nov 17;21(22):8657. doi: 10.3390/ijms21228657.
Cannabinoid type 1 receptor (CBR) is expressed and participates in several aspects of cerebral cortex embryonic development as demonstrated with whole-transcriptome mRNA sequencing and other contemporary methods. However, the cellular location of CBR, which helps to specify molecular mechanisms, remains to be documented. Using three-dimensional (3D) electron microscopic reconstruction, we examined CBR immunolabeling in proliferating neural stem cells (NSCs) and migrating neurons in the embryonic mouse () and rhesus macaque () cerebral cortex. We found that the mitotic and postmitotic ventricular and subventricular zone (VZ and SVZ) cells are immunonegative in both species while radially migrating neurons in the intermediate zone (IZ) and cortical plate (CP) contain CBR-positive intracellular vesicles. CBR immunolabeling was more numerous and more extensive in monkeys compared to mice. In CBR-knock out mice, projection neurons in the IZ show migration abnormalities such as an increased number of lateral processes. Thus, in radially migrating neurons CBR provides a molecular substrate for the regulation of cell movement. Undetectable level of CBR in VZ/SVZ cells indicates that previously suggested direct CBR-transmitted regulation of cellular proliferation and fate determination demands rigorous re-examination. More abundant CBR expression in monkey compared to mouse suggests that therapeutic or recreational cannabis use may be more distressing for immature primate neurons than inferred from experiments with rodents.
大麻素受体 1（CBR）在大脑皮层胚胎发育的多个方面表达并参与其中，这已通过全转录组 mRNA 测序和其他现代方法得到证实。然而，有助于确定分子机制的 CBR 细胞位置仍有待记录。使用三维（3D）电子显微镜重建，我们检查了胚胎期小鼠（）和恒河猴（）大脑皮层中增殖神经干细胞（NSC）和迁移神经元中的 CBR 免疫标记。我们发现，两种物种的有丝分裂和有丝分裂后室下区（VZ 和 SVZ）细胞均为免疫阴性，而中间区（IZ）和皮质板（CP）中的放射状迁移神经元含有 CBR 阳性细胞内囊泡。与小鼠相比，猴子中的 CBR 免疫标记更多且更广泛。在 CBR 敲除小鼠中，IZ 中的投射神经元显示出迁移异常，例如侧突数量增加。因此，在放射状迁移神经元中，CBR 为细胞运动的调节提供了分子基础。VZ/SVZ 细胞中无法检测到 CBR 水平表明，先前提出的直接 CBR 传递的细胞增殖和命运决定的调节需要严格重新检查。与小鼠相比，猴子中 CBR 的表达更为丰富，这表明治疗或娱乐性大麻的使用可能对未成熟灵长类神经元的影响比从啮齿动物实验中推断的更为严重。
