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.

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