Udagawa Jun, Hashimoto Ryuju, Hioki Kyoji, Otani Hiroki
Research Project Promotion Institute, Shimane University, Izumo 693-8501, Japan.
Brain Res. 2006 Nov 20;1120(1):74-82. doi: 10.1016/j.brainres.2006.08.116. Epub 2006 Oct 3.
Leptin is an obese gene product that decreases appetite and raises energy expenditure in adults. We previously reported that leptin was detected in the sera of mouse embryos and leptin receptors were expressed in the mouse embryonic cerebrum, suggesting that leptin plays a role in cerebral development. In this study, we injected leptin into the lateral ventricle of the cerebrum in leptin-deficient ob/ob mouse embryos to investigate the function of leptin in cerebral development. When leptin was injected on embryonic day (E) 14, the ratio of the number of cells in the cortical plate (CP) to that in the intermediate zone (IZ) was higher in leptin-injected than in vehicle-injected ob/ob embryos on E16, although there was no significant difference in the number of cells in the ventricular zone (VZ), IZ, or CP between these groups. The number of postmitotic BrdU-positive CP cells was larger in leptin-injected than in vehicle-injected ob/ob embryos on E16 and E17 when BrdU labeling and leptin injection were performed on E14. By in situ hybridization, NPY mRNA expression in CP neurons on E18 was weaker in leptin-injected than in vehicle-injected ob/ob embryos when leptin was injected on E16. These results suggest that leptin promotes the migration of neuronal lineage cells to CP and that the leptin-NPY axis in neurons works in the cerebral cortex on E16.
瘦素是一种肥胖基因产物，可降低成年人的食欲并提高能量消耗。我们之前报道过，在小鼠胚胎血清中检测到了瘦素，且瘦素受体在小鼠胚胎大脑中表达，这表明瘦素在大脑发育中发挥作用。在本研究中，我们将瘦素注射到瘦素缺陷型ob/ob小鼠胚胎大脑的侧脑室中，以研究瘦素在大脑发育中的功能。当在胚胎第（E）14天注射瘦素时，在E16时，注射瘦素的ob/ob胚胎皮质板（CP）中的细胞数量与中间带（IZ）中的细胞数量之比高于注射溶剂的ob/ob胚胎，尽管这些组之间脑室区（VZ）、IZ或CP中的细胞数量没有显著差异。当在E14进行BrdU标记和瘦素注射时，在E16和E17时，注射瘦素的ob/ob胚胎中处于有丝分裂后BrdU阳性的CP细胞数量多于注射溶剂的ob/ob胚胎。通过原位杂交，当在E16注射瘦素时，在E18时，注射瘦素的ob/ob胚胎中CP神经元的NPY mRNA表达比注射溶剂的ob/ob胚胎弱。这些结果表明，瘦素促进神经谱系细胞向CP迁移，并且神经元中的瘦素-NPY轴在E16时在大脑皮层中起作用。
