Ransome M I, Turnley A M
Neural Regeneration Laboratory, Centre for Neuroscience, University of Melbourne, Melbourne, Victoria 3010, Australia.
Neuroscience. 2005;132(3):673-87. doi: 10.1016/j.neuroscience.2004.12.041.
Developing an understanding of factors that regulate development of the nervous system is important if we hope to be able to repair the nervous system after injury or disease. Suppressor of cytokine signaling-2 (SOCS2) is an intracellular regulator of cytokine signaling that blocks the inhibitory effects of growth hormone on neuronal differentiation and promotes neurogenesis. Here we examine the effect of SOCS2 over-expression on brain development by assessing density and soma size of different neuronal populations in the somatosensory cortex and striatum of SOCS2 transgenic mice compared with wildtype C57BL/6 mice. There were no significant differences in brain weight, cortical thickness or striatal area between mice of either genotype. Analysis of NeuN positive neuronal cell density showed a modest but significant 9% increase across layers 2-6 of SOCS2 transgenic cortex, while cortical interneuron subpopulations were variably affected. In the cortex, parvalbumin and somatostatin expressing neuron densities were unaffected, while calretinin and calbindin positive neuronal densities increased by 48% and 45% respectively. There was no apparent difference in glial fibrillary acidic protein positive astrocyte numbers in layers 1 or 6b of cortex. Furthermore, soma sizes of calretinin and calbindin positive cortical neurons were significantly smaller than wildtype, although there was no difference in size of Cresyl Violet-stained layer 5 projection neurons nor of parvalbumin or somatostatin positive cortical neurons. Additionally, synaptic density and dendritic branching were found to be increased in SOCS2 transgenic cortex. These effects on calretinin and calbindin positive cortical neurons and cortical neuronal circuitry were not observed in the striatum of SOCS2-Tg brains. However, striatal cholinergic interneurons were significantly smaller in SOCS2-Tg brains. At embryonic day 14.5, proliferation and apoptosis in the developing telencephalon were similar in each genotype. Therefore, over-expression of SOCS2 variably affects different cortical regions and neuronal populations, with the predominant effect appearing to be on interneurons and neuronal connectivity in the cortex.
如果我们希望能够在损伤或疾病后修复神经系统，那么了解调节神经系统发育的因素就很重要。细胞因子信号转导抑制因子2（SOCS2）是细胞因子信号转导的细胞内调节因子，它能阻断生长激素对神经元分化的抑制作用并促进神经发生。在这里，我们通过评估SOCS2转基因小鼠与野生型C57BL/6小鼠体感皮层和纹状体中不同神经元群体的密度和胞体大小，来研究SOCS2过表达对大脑发育的影响。两种基因型小鼠的脑重量、皮层厚度或纹状体面积均无显著差异。对NeuN阳性神经元细胞密度的分析显示，SOCS2转基因皮层第2 - 6层的密度有适度但显著的9%增加，而皮层中间神经元亚群受到不同程度的影响。在皮层中，表达小白蛋白和生长抑素的神经元密度未受影响，而表达钙视网膜蛋白和钙结合蛋白的神经元密度分别增加了48%和45%。皮层第1层或第6b层中胶质纤维酸性蛋白阳性星形胶质细胞数量没有明显差异。此外，表达钙视网膜蛋白和钙结合蛋白的皮层神经元胞体大小明显小于野生型，尽管硫堇染色的第5层投射神经元以及表达小白蛋白或生长抑素的皮层神经元大小没有差异。此外，发现SOCS2转基因皮层中的突触密度和树突分支增加。在SOCS2转基因大脑的纹状体中未观察到对表达钙视网膜蛋白和钙结合蛋白的皮层神经元以及皮层神经元回路的这些影响。然而，SOCS2转基因大脑中的纹状体胆碱能中间神经元明显较小。在胚胎第14.5天，每种基因型发育中的端脑中的增殖和凋亡情况相似。因此，SOCS2的过表达对不同的皮层区域和神经元群体有不同程度的影响，主要影响似乎是对皮层中的中间神经元和神经元连接性。
