The effect of brain-derived neurotrophic factor on radiation-induced neuron architecture impairment is associated with the NFATc4/3 pathway

Irradiation to developing brains results in progressive cognitive dysfunction. Changes in the morphology of mature neurons are thought to be related to impairments of cognitive function. However, little is known about the effects of radiation on neurite outgrowth of immature neurons. Therefore, we sought to evaluate the structural alterations of immature neurons following X-ray irradiation and determine potential strategies to reverse it. Our data revealed damage to the neurite outgrowths of cultured neurons after 2 Gy and 8 Gy irradiation at 1 d and 3 d, respectively. De-phosphorylation of nuclear factor of activated T-cells c4/3 (NFATc4/3) was inhibited post-irradiation. Extraneous brain-derived neurotrophic factor (BDNF) ameliorated impairment of neurite growth and activated the NFATc4/3 signaling pathway. These data indicate that BDNF confers neuroprotective effects against irradiation by modulating the NFATc4/3 pathway.