Madsen T M, Kristjansen P E G, Bolwig T G, Wörtwein G
Laboratory of Neuropsychiatry, Department of Psychiatry O-6102, H:S Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Neuroscience. 2003;119(3):635-42. doi: 10.1016/s0306-4522(03)00199-4.
The generation of new neurons in the adult mammalian brain has been documented in numerous recent reports. Studies undertaken so far indicate that adult hippocampal neurogenesis is related in a number of ways to hippocampal function.Here, we report that subjecting adult rats to fractionated brain irradiation blocked the formation of new neurons in the dentate gyrus of the hippocampus. At different time points after the termination of the irradiation procedure, the animals were tested in two tests of short-term memory that differ with respect to their dependence on hippocampal function. Eight and 21 days after irradiation, the animals with blocked neurogenesis performed poorer than controls in a hippocampus-dependent place-recognition task, indicating that the presence of newly generated neurons may be necessary for the normal function of this brain area. The animals were never impaired in a hippocampus-independent object-recognition task. These results are in line with other reports documenting the functional significance of newly generated neurons in this region. As our irradiation procedure models prophylactic cranial irradiation used in the treatment of different cancers, we suggest that blocked neurogenesis contributes to the reported deleterious side effects of this treatment, consisting of memory impairment, dysphoria and lethargy.
近期众多报告已证实成年哺乳动物大脑中会生成新的神经元。迄今为止开展的研究表明，成年海马体神经发生在许多方面与海马体功能相关。在此，我们报告对成年大鼠进行分次脑部照射会阻碍海马体齿状回中新神经元的形成。在照射程序结束后的不同时间点，对动物进行两项短期记忆测试，这两项测试在对海马体功能的依赖程度上有所不同。照射后8天和21天，神经发生受阻的动物在依赖海马体的位置识别任务中的表现比对照组差，这表明新生成神经元的存在可能是该脑区正常功能所必需的。这些动物在不依赖海马体的物体识别任务中从未受损。这些结果与其他记录该区域新生成神经元功能意义的报告一致。由于我们的照射程序模拟了用于治疗不同癌症的预防性颅脑照射，我们认为神经发生受阻会导致这种治疗所报告的有害副作用，包括记忆障碍、烦躁不安和嗜睡。
