THE FOCAL BRAIN PROTON BEAM IRRADIATION INSULT IN RATS – INDUCED MEMORY DISTURBANCE RELATED CHANGE IN ACETYLCHOLINE RECEPTOR BINDING
THE FOCAL BRAIN PROTON BEAM IRRADIATION INSULT IN RATS – INDUCED MEMORY DISTURBANCE RELATED CHANGE IN ACETYLCHOLINE RECEPTOR BINDING
复制标题
局灶性脑质子束照射对大鼠的损害——诱发记忆障碍相关的乙酰胆碱受体结合变化
DOI：
10.21175/radproc.2017.06
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发表时间：
2017
影响因子：
3.5
通讯作者：
Y. Ohba
中科院分区：
文献类型：
--
作者：
N. Takai;Masatsugu Ohgami;K. Ando;A. Uzawa;R. Hirayama;Saori Nakamura;Y. Ohba
脑功能障碍是与脑肿瘤放射治疗相关的主要问题之一。然而，人们对质子照射引起的脑功能障碍的神经化学基础知之甚少。我们在这里研究了质子束引起的脑损伤的早期后果。用 70 MeV 质子束局部照射雄性 Wistar 大鼠的大脑。照射剂量设定为已知会产生血管变化并随后发生坏死的水平，这种变化出现在30Gy照射后的后期。在受辐射的大鼠中使用八臂径向迷宫任务。为了评估记忆的保存（回忆），表现出空间认知能力的老鼠受到了辐射。与对照组大鼠相比，照射后24小时，未观察到受照射大鼠的保存记忆受损。正确选择和错误数量的双向方差分析的重复测量显示对照组和 30 Gy 照射组之间没有差异。为了评估水迷宫中平台位置的记忆和工作记忆的获取过程，在照射后24小时开始任务。在学习任务（记忆的获取过程）中，对照组和照射组的平台潜伏期没有差异。对记忆了标准位置位置的大鼠进行照射，照射后24小时与对照大鼠相比，未观察到受照射大鼠的长期记忆受损。然而，当平台放置在非标准位置时，受辐射的大鼠比对照大鼠需要更长的时间才能找到平台。由此可见，30 Gy 的质子剂量会损害大鼠的工作记忆。使用放射性配体苯甲酸奎宁环酯 ([3H]QNB) 通过体内结合测定分析毒蕈碱乙酰胆碱受体的功能。照射后24小时，对受照射的大鼠静脉注射5.5MBq的[3H]QNB。放射自显影研究表明，在质子照射后的早期阶段，[3H]QNB 体内结合发生了过渡性增加。另一方面，在受辐射大鼠脑切片的放射自显影图中未观察到体外[3H]QNB结合的变化。照射后5个月或6个月时出现脑血流量和脑部组织病理学变化。这些结果表明，辐射引起的行为障碍与体内条件下可检测到的受体功能的早期变化密切相关。
Cerebral dysfunction is one of the major concerns associated with radiotherapy of brain tumours. However, little is known about the neurochemical basis of brain dysfunction induced by proton irradiation. We here investigated the early consequences of brain damages caused by a proton beam. Brains of male wistar rats were locally irradiated with a 70 MeV proton beam. The irradiation dose was set at level known to produce vascular change followed by necrosis, which appeared the late period after irradiation with 30 Gy. The eight-arm radial maze task in irradiated rats was used. In order to assess the preservation (recall) of memory, the rats that showed the spatial cognition were irradiated. The impairment of the preservation memory was not observed in the irradiated rats compared to the control ones 24 hrs after irradiation. Repeated measures of two-way ANOVA of correct choices and number of errors showed no differences between the control group and 30 Gy irradiated group. In order to assess the acquisition process of memory and working memory for the platform location in the water maze, the task was started on the 24 hrs after irradiation. In the learning task (the acquisition process of memory), there was no difference between the control group and irradiated group in the latency to platform. The rats that memorized the location of the standard position were irradiated, and the impairment of the long-term memory was not observed in the irradiated rats compared to the control ones 24 hrs after irradiation. However, the irradiated rats required a substantially longer time finding out the platform than the control rats when the platform was placed in a non-standard position. From this it follows that a proton dose of 30 Gy impaired the working memory of rats. The function of muscarinic acetylcholine receptors was analyzed by in vivo binding assay using radioligand quinuclidinyl benzilate ([3H]QNB). The irradiated rats were intravenously injected with 5.5 MBq of [3H]QNB on the 24 hrs after the irradiation. Autoradiographic studies showed a transitional increase of [3H]QNB in-vivo binding in the early phase after proton irradiation. On the other hand, no change in in-vitro [3H]QNB binding was seen in the autoradiogram of brain slices from the irradiated rats. The cerebral blood flow and the histopathological change in the brain appeared at 5 or 6 months after irradiation. These results indicate that the relation between behavioral impairment caused by radiation is closely related to the early change in the receptor function which could be detected in in-vivo conditions.
影响因子：
11.2
作者：
S. Mizumatsu;Michelle Monje;Duncan R. Morhardt;R. Rola;T. Palmer;J. Fike
通讯作者：
S. Mizumatsu;Michelle Monje;Duncan R. Morhardt;R. Rola;T. Palmer;J. Fike
影响因子：
5.3
作者：
Zola, SM;Squire, LR;Clark, RE
通讯作者：
Clark, RE