Regulation of Axonal Elongation and Pathfinding from the Entorhinal Cortex to the Dentate Gyrus in the Hippocampus by the Chemokine Stromal Cell-Derived Factor 1α
Regulation of Axonal Elongation and Pathfinding from the Entorhinal Cortex to the Dentate Gyrus in the Hippocampus by the Chemokine Stromal Cell-Derived Factor 1α
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DOI：
10.1523/jneurosci.1670-08.2008
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发表时间：
2008-08
期刊：
影响因子：
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通讯作者：
Yoichi Ohshima;T. Kubo;R. Koyama;M. Ueno;Masanori Nakagawa;T. Yamashita
中科院分区：
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作者：
Yoichi Ohshima;T. Kubo;R. Koyama;M. Ueno;Masanori Nakagawa;T. Yamashita
在发育早期，内嗅皮层（EC）和海马齿状回（DG）之间通过穿通通路建立起神经回路。然而，穿通纤维的导航方式大多仍然是一个谜。在这里，我们分析了趋化因子，即基质细胞衍生因子1α（SDF-1α），在穿通纤维导航的功能作用。SDF-1α可促进出生后第0天大鼠培养的内嗅皮层神经元中依赖于mDia 1的神经突生长。然后，我们使用包括绿色荧光标记的EC和DG切片的内鼻-海马共培养物来评估EC的穿通纤维的投射。虽然用该系统观察到内嗅轴突的特异性层状终止，但当SDF-1α信号通路被针对SDF-1α的中和抗体或特异性SDF-1α受体拮抗剂AMD 3100（1，1 ′-[1，4-亚苯基双（亚甲基）]双-1，4，8，1,1-四氮杂环十四烷八盐酸盐）阻断时，适当终止的内嗅轴突数量显著减少。此外，SDF-1α信号通路的抑制导致DG中PSD-95（突触后密度蛋白-95）的免疫反应性降低，这可能是因为投射的穿通纤维数量减少。这些结果表明，SDF-1α在促进从EC到DG的穿通纤维的生长中起关键作用。
During the early developmental stage, a neural circuit is established between the entorhinal cortex (EC) and the hippocampal dentate gyrus (DG) via the perforant pathway. However, the manner in which the perforant fibers are navigated has mostly remained a mystery. Here, we analyzed the functional role of a chemokine, namely, stromal cell-derived factor 1α (SDF-1α), in the navigation of the perforant fibers. SDF-1α was observed to promote neurite growth, which is dependent on mDia1, in cultured entorhinal cortical neurons obtained from rats at postnatal day 0. We then used entorhino-hippocampal cocultures comprising green fluorescence-labeled EC and DG slices to assess the projection of the perforant fibers from the EC. Although the specific laminar termination of the entorhinal axons was observed with this system, the number of appropriately terminating entorhinal axons decreased significantly when the SDF-1α signaling pathway was blocked by a neutralizing antibody against SDF-1α or by the specific SDF-1α receptor antagonist AMD3100 (1,1′-[1,4-phenylenebis(methylene)]bis-1,4,8,11-tetra-azacyclotetradecane octahydrochloride). Furthermore, inhibition of the SDF-1α signaling pathway resulted in a decrease in the immunoreactivity for PSD-95 (postsynaptic density protein-95) in the DG, possibly because of a reduction in the number of projecting perforant fibers. These results demonstrate that SDF-1α plays a critical role in promoting the growth of perforant fibers from the EC to the DG.