Environmental enrichment enhances neurogenesis and improves functional outcome after cranial irradiation
Environmental enrichment enhances neurogenesis and improves functional outcome after cranial irradiation
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DOI：
10.1111/j.1460-9568.2006.05269.x
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发表时间：
2007-01-01
影响因子：
3.4
通讯作者：
Liu, Jialing
中科院分区：
文献类型：
--
作者：
Fan, Yang;Liu, Zhengyan;Liu, Jialing
放射治疗是一种广泛用于脑肿瘤的治疗方法，但它可能导致延迟的进行性认知衰退和记忆缺陷。先前的研究表明，这种神经认知功能障碍可能与海马神经发生损伤有关。然而，关于如何减少放射治疗引起的认知障碍，人们知之甚少。为了研究环境富集（environmental enrichment， EE）是否促进辐照后的神经发生和认知功能，我们将沙鼠置于环境富集环境中2个月，通过神经行为测试和神经发生免疫组织化学分析来评估它们的学习记忆功能。我们的研究结果表明，即使是相对低剂量（5-10 Gy）的辐射也能使齿状回的前体细胞增殖急剧减少90%以上。这种前体细胞增殖的减少是持续的，并导致9个月后颗粒细胞数量的显著下降。EE外壳增加了新生神经元的数量，增加了残余神经发生。EE还显著增加了齿状回未成熟神经元的总数。此外，在5天的训练中，受辐射的动物在水迷宫测试中表现出空间学习和记忆的显著改善，在旋转运动学习方面也有显著改善。综上所述，情感表达对受辐射沙鼠成年海马神经发生和功能恢复有积极影响。我们的数据表明，辐射损伤后的成年动物海马祖细胞仍有相当数量的可塑性，可以成为辐射诱导认知功能障碍治疗干预的靶点。
Radiation therapy is a widely used treatment for brain tumors but it can cause delayed progressive cognitive decline and memory deficits. Previous studies suggested that this neurocognitive dysfunction might be linked to the impairment of hippocampal neurogenesis. However, little is known regarding how to reduce the cognitive impairment caused by radiation therapy. To investigate whether environmental enrichment (EE) promotes neurogenesis and cognitive function after irradiation, irradiated gerbils were housed in EE for 2 months and evaluated by neurobehavioral testing for learning and memory function, and immunohistochemical analysis for neurogenesis. Our results demonstrated that even relatively low doses (5-10 Gy) of irradiation could acutely abolish precursor cell proliferation in the dentate gyrus by more than 90%. This reduction in precursor proliferation was persistent and led to a significant decline in the granule cell population 9 months later. EE housing enhanced the number of newborn neurons and increased residual neurogenesis. EE also significantly increased the total number of immature neurons in the dentate gyrus. Furthermore, irradiated animals after EE housing showed a significant improvement in spatial learning and memory during the water-maze test and in rotorod motor learning over a 5-day training paradigm. In conclusion, EE has a positive impact on hippocampal neurogenesis and functional recovery in irradiated adult gerbils. Our data suggest that there is still a considerable amount of plasticity remaining in the hippocampal progenitor cells in adult animals after radiation injury, which can become a target of therapeutic intervention for radiation-induced cognitive dysfunction.