Depletion of new neurons by image guided irradiation
Depletion of new neurons by image guided irradiation
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DOI：
10.3389/fnins.2011.00059
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发表时间：
2011-01-01
影响因子：
4.3
通讯作者：
Wojtowicz, J. M.
中科院分区：
文献类型：
--
作者：
Tan, Y. -F.;Rosenzweig, S.;Wojtowicz, J. M.
电离辐射仍然是成像和治疗癌症的相关工具。局灶照射的实验用途最近已扩大到研究成人大脑中的新神经元。这些研究表明，放射治疗后会出现认知缺陷，并对可能发生在人类身上的意外影响提出了警告。辐照对成人神经发生影响的相互矛盾的结果表明，这种影响要么是短暂的，要么是永久性的。在这项研究中，我们使用了用于治疗人类肿瘤的辐照装置来评估辐射对大鼠神经发生的影响。我们使用麻醉下的成年雄性大鼠（Sprague-Dawley）作为研究对象。辐照束指向海马，一个学习和记忆的中心，也是成人大脑中神经源性活动的部位。照射剂量率为0.6 Gy/min，剂量范围为0.5 Gy至10.0 Gy。这些动物被放回家里的笼子里，没有任何副作用的迹象。在照射后1周或6周测量神经发生情况。1周时，神经元祖细胞数量呈剂量依赖性减少，0.78 Gy时减少50%。剂量-反应曲线用双指数拟合得很好，表明两个过程。定量免疫组织化学检查显示，低剂量对神经元祖细胞有明显影响，导致80%的神经发生抑制。这种效应是部分可逆的，可能是由于剩余前体的代偿性增殖。在高剂量（bbb50 Gy）下，有额外的，几乎完全的神经发生阻滞，没有代偿性增殖。我们的结论是，尽管辐照对实验目的有用，但人类受试者暴露于放射治疗中常用的剂量可能具有破坏性并导致认知障碍。
Ionizing radiation continues to be a relevant tool in both imaging and the treatment of cancer. Experimental uses of focal irradiation have recently been expanded to studies of new neurons in the adult brain. Such studies have shown cognitive deficits following radiation treatment and raised caution as to possible unintentional effects that may occur in humans. Conflicting outcomes of the effects of irradiation on adult neurogenesis suggest that the effects are either transient or permanent. In this study, we used an irradiation apparatus employed in the treatment of human tumors to assess radiation effects on rat neurogenesis. For subjects we used adult male rats (Sprague-Dawley) under anesthesia. The irradiation beam was directed at the hippocampus, a center for learning and memory, and the site of neurogenic activity in adult brain. The irradiation was applied at a dose-rate 0.6 Gy/min for total single-fraction, doses ranging from 0.5 to 10.0 Gy. The animals were returned to home cages and recovered with no sign of any side effects. The neurogenesis was measured either 1 week or 6 weeks after the irradiation. At 1 week, the number of neuronal progenitors was reduced in a dose-dependent manner with the 50% reduction at 0.78 Gy. The dose-response curve was well fitted by a double exponential suggesting two processes. Examination of the tissue with quantitative immunohistochemistry revealed a dominant low-dose effect on neuronal progenitors resulting in 80% suppression of neurogenesis. This effect was partially reversible, possibly due to compensatory proliferation of the remaining precursors. At higher doses (>5 Gy) there was additional, nearly complete block of neurogenesis without compensatory proliferation. We conclude that notwithstanding the usefulness of irradiation for experimental purposes, the exposure of human subjects to doses often used in radiotherapy treatment could be damaging and cause cognitive impairments.