The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China.
Institute of Radiotherapy and Oncology, Soochow University, Suzhou, Jiangsu, China.
Radiat Res. 2019 Sep;192(3):345-351. doi: 10.1667/RR15409.1. Epub 2019 Jul 11.
Stem cell transplantation is thought to be an effective method for radiation-induced cognitive dysfunction. However, there have been few studies performed to determine whether transplanted stem cells can integrate into hippocampus circuits. Brain-derived neurotrophic factor (BDNF) plays a critical role in brain development. Therefore, we investigated the differentiation and integration of brain-derived neurotrophic factor overexpressing neural stem cells (NSCs). We observed that these transplanted cells migrated to the subgranular zone of irradiated rats at 4 weeks after transplantation. However, control neural stem cells were disordered, distributing in the irradiated hippocampus, and showed greater astroglia differentiation tendency. Retrograde monosynaptic tracing showed that neurons derived from transplanted brain-derived neurotrophic factor overexpressing neural stem cells integrated into the circuit better than those from control cells. Brain-derived neurotrophic factor overexpressing neural stem cells s promoted the expression of brain-derived neurotrophic factor and nerve growth factor and reduced the number of activated microglia caused by radiation. Transplanted brain-derived neurotrophic factor overexpressing neural stem cells failed to improve radiation-induced cognitive dysfunction. These results indicate that brain-derived neurotrophic factor overexpressing neural stem cells suffered less from changed microenvironment after irradiation and possessed the ability to improve the host niche. Neurons derived from Brain-derived neurotrophic factor overexpressing neural stem cells showed the integration potency in the irradiated hippocampus.
干细胞移植被认为是一种治疗放射性认知功能障碍的有效方法。然而，目前很少有研究确定移植的干细胞是否能整合到海马回路中。脑源性神经营养因子（BDNF）在大脑发育中起着至关重要的作用。因此，我们研究了过表达脑源性神经营养因子的神经干细胞（NSCs）的分化和整合。我们观察到，这些移植细胞在移植后 4 周迁移到照射大鼠的颗粒下区。然而，对照神经干细胞排列紊乱，分布在照射的海马区，表现出更大的星形胶质细胞分化倾向。逆行单突触追踪显示，源自移植的过表达脑源性神经营养因子的神经干细胞比源自对照细胞的神经干细胞更好地整合到回路中。过表达脑源性神经营养因子的神经干细胞促进了脑源性神经营养因子和神经生长因子的表达，并减少了辐射引起的小胶质细胞激活的数量。移植的过表达脑源性神经营养因子的神经干细胞未能改善辐射引起的认知功能障碍。这些结果表明，过表达脑源性神经营养因子的神经干细胞在照射后较少受到改变的微环境的影响，并且具有改善宿主小生境的能力。源自过表达脑源性神经营养因子的神经干细胞的神经元在照射的海马区表现出整合潜能。
