Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
Department of Brain Tumor Biology, Brain Research Institute, Niigata University, Niigata, Japan.
Neurochem Res. 2022 Sep;47(9):2632-2644. doi: 10.1007/s11064-021-03524-6. Epub 2022 Jan 4.
Neuronal differentiation, maturation, and synapse formation are regulated by various growth factors. Here we show that epidermal growth factor (EGF) negatively regulates presynaptic maturation and synapse formation. In cortical neurons, EGF maintained axon elongation and reduced the sizes of growth cones in culture. Furthermore, EGF decreased the levels of presynaptic molecules and number of presynaptic puncta, suggesting that EGF inhibits neuronal maturation. The reduction of synaptic sites is confirmed by the decreased frequencies of miniature EPSCs. In vivo analysis revealed that while peripherally administrated EGF decreased the levels of presynaptic molecules and numbers of synaptophysin-positive puncta in the prefrontal cortices of neonatal rats, EGF receptor inhibitors upregulated these indexes, suggesting that endogenous EGF receptor ligands suppress presynaptic maturation. Electron microscopy further revealed that EGF decreased the numbers, but not the sizes, of synaptic structures in vivo. These findings suggest that endogenous EGF and/or other EGF receptor ligands negatively modulates presynaptic maturation and synapse formation.
神经元的分化、成熟和突触形成受多种生长因子调节。在这里，我们发现表皮生长因子（EGF）负调控突触前成熟和突触形成。在皮质神经元中，EGF 维持轴突伸长并减小培养中的生长锥的大小。此外，EGF 降低了突触前分子的水平和突触前突触点的数量，表明 EGF 抑制神经元成熟。突触部位的减少通过减少微小 EPSC 的频率得到证实。体内分析表明，虽然外周给予 EGF 会降低新生大鼠前额皮质中突触前分子的水平和突触小泡蛋白阳性突触点的数量，但 EGF 受体抑制剂上调了这些指标，表明内源性 EGF 受体配体抑制突触前成熟。电子显微镜进一步显示，EGF 减少了体内突触结构的数量，但不改变其大小。这些发现表明，内源性 EGF 和/或其他 EGF 受体配体负调控突触前成熟和突触形成。
