Implanted cannula-mediated repetitive administration of Aβ25–35 into the mouse cerebral ventricle effectively impairs spatial working memory
Implanted cannula-mediated repetitive administration of Aβ25–35 into the mouse cerebral ventricle effectively impairs spatial working memory
复制标题
DOI：
10.1016/j.bbr.2005.03.026
复制
发表时间：
2005-11
影响因子：
2.7
通讯作者：
M. Yamada;T. Chiba;J. Sasabe;Mikiro Nawa;H. Tajima;T. Niikura;K. Terashita;S. Aiso;Y. Kita;M. Matsuoka;I. Nishimoto
中科院分区：
文献类型：
--
作者：
M. Yamada;T. Chiba;J. Sasabe;Mikiro Nawa;H. Tajima;T. Niikura;K. Terashita;S. Aiso;Y. Kita;M. Matsuoka;I. Nishimoto
淀粉样蛋白β (Aβ)与阿尔茨海默病（AD）的发病密切相关。为了构建阿尔茨海默病动物模型，在早期的研究中已经进行了向啮齿动物脑室灌注大剂量毒性a β的实验。同时，一种通过渗透泵进入脑室的连续输注系统已被开发用于制造大鼠AD模型。在这项研究中，我们通过脑室插管反复给药a β25 - 35，建立了小鼠AD模型。利用该管理系统，我们可重复构建空间工作记忆受损小鼠。根据小鼠异常行为的发生，我们发现a β25 - 35给药小鼠脑室旁区胆碱乙酰转移酶（ChAT）阳性神经元数量呈剂量依赖性减少。考虑到通过植入式插管反复给药小剂量的有毒a β比一次性大剂量注射a β更接近AD患者的大脑状态，并且治疗药物和毒性药物能够通过植入式插管反复可靠地给药，我们得出结论，植入式插管携带AD小鼠模型有助于开发新的AD治疗方法。
Amyloid β (Aβ) is closely related to the onset of Alzheimer's disease (AD). To construct AD animal models, a bolus administration of a large dose of toxic Aβ into the cerebral ventricles of rodents has been performed in earlier studies. In parallel, a continuous infusion system via an osmotic pump into the cerebral ventricle has been developed to make a rat AD model. In this study, we developed a mouse AD model by repetitive administration of Aβ25–35 via a cannula implanted into the cerebral ventricle. Using this administration system, we reproducibly constructed a mouse with impaired spatial working memory. In accordance with the occurrence of the abnormal mouse behavior, we found that the number of choline acetyltransferase (ChAT)-positive neurons was reduced in paraventricular regions of brains of Aβ25–35-administered mice in a dose-dependent manner. Considering that the repetitive administration of a small dose of toxic Aβ via an implanted cannula leads to a brain status more resembling that of the AD patients than a bolus injection of a large dose of Aβ, and therapeutic as well as toxic agents are able to be repeatedly and reliably administered via an implanted cannula, we concluded that the implanted cannula-bearing AD mouse model is useful for development of new AD therapy.