Naylor Andrew S, Bull Cecilia, Nilsson Marie K L, Zhu Changlian, Björk-Eriksson Thomas, Eriksson Peter S, Blomgren Klas, Kuhn H Georg
Center for Brain Repair and Rehabilitation, Sahlgrenska Academy, University of Gothenburg, Box 432, 405 30, Sweden.
Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14632-7. doi: 10.1073/pnas.0711128105. Epub 2008 Sep 2.
Cranial radiation therapy is commonly used in the treatment of childhood cancers. It is associated with cognitive impairments tentatively linked to the hippocampus, a neurogenic region of the brain important in memory function and learning. Hippocampal neurogenesis is positively regulated by voluntary exercise, which is also known to improve hippocampal-dependent cognitive functions. In this work, we irradiated the brains of C57/BL6 mice on postnatal day 9 and evaluated both the acute effects of irradiation and the effects of voluntary running on hippocampal neurogenesis and behavior 3 months after irradiation. Voluntary running significantly restored precursor cell and neurogenesis levels after a clinically relevant, moderate dose of irradiation. We also found that irradiation perturbed the structural integration of immature neurons in the hippocampus and that this was reversed by voluntary exercise. Furthermore, irradiation-induced behavior alterations observed in the open-field test were ameliorated. Together, these results clearly demonstrate the usefulness of physical exercise for functional and structural recovery from radiation-induced injury to the juvenile brain, and they suggest that exercise should be evaluated in rehabilitation therapy of childhood cancer survivors.
颅脑放射治疗常用于儿童癌症的治疗。它与认知障碍有关，这些认知障碍初步被认为与海马体有关，海马体是大脑中一个对记忆功能和学习很重要的神经发生区域。海马体神经发生受到自愿运动的正向调节，而自愿运动也已知能改善依赖海马体的认知功能。在这项研究中，我们在出生后第9天对C57/BL6小鼠的大脑进行照射，并评估照射的急性效应以及照射3个月后自愿跑步对海马体神经发生和行为的影响。在临床相关的中等剂量照射后，自愿跑步显著恢复了前体细胞和神经发生水平。我们还发现，照射扰乱了海马体中未成熟神经元的结构整合，而这种情况通过自愿运动得到了逆转。此外，在旷场试验中观察到的照射诱导的行为改变也得到了改善。总之，这些结果清楚地证明了体育锻炼对幼年大脑辐射损伤后的功能和结构恢复的有用性，并且表明在儿童癌症幸存者的康复治疗中应评估运动的作用。
