Bilateral Injections of Amyloid-β 25-35 into the Amygdala of Young Fischer Rats: Behavioral, Neurochemical, and Time Dependent Histopathological Effects
Bilateral Injections of Amyloid-β 25-35 into the Amygdala of Young Fischer Rats: Behavioral, Neurochemical, and Time Dependent Histopathological Effects
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将淀粉样蛋白-β 25-35 双侧注射到幼年费舍尔大鼠的杏仁核中：行为、神经化学和时间依赖性组织病理学效应
DOI：
10.1016/s0197-4580(97)00154-1
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发表时间：
1997
影响因子：
4.2
通讯作者：
S. Lorens
中科院分区：
文献类型：
--
作者：
E.M Sigurdsson;J.M Lee;Xin;M. Hejna;S. Lorens
为了检查双侧注射淀粉样蛋白-β 25-35 (Aβ) 的组织病理学效应的时间过程，并确定这些效应是否与胆碱乙酰转移酶活性降低和行为障碍相关，我们将 Aβ (5.0 nmol) 注射到年轻雄性 Fischer 大鼠的杏仁核中。对照大鼠接受媒介物输注。为了进行组织学分析，在术后 8、32、64、96 和 128 天处死动物（每个时间点 n = 21-33）。 Aβ 诱导右侧杏仁核和海马神经元 tau-2 染色，但不诱导左侧杏仁核和海马。 Aβ 还分别诱导右侧海马和杏仁核内的反应性星形细胞增多和神经元萎缩。与 tau-2 一样，Aβ 治疗大鼠左半球内的这些相同大脑区域受到的影响明显较小。此外，Aβ 似乎还能诱导小胶质细胞和神经元白细胞介素 1β 染色。 Aβ 的组织病理学效应在术后 32 天达到峰值，但与杏仁核胆碱乙酰转移酶活性的降低无关。在一项单独的实验中，分析了术后 34-52 天双侧杏仁核内注射 Aβ 的行为影响。在旷场测试中，处理组仅在发出的尾声数量上有所不同（p = 0.016）。 Aβ 对莫里斯水迷宫或单向条件性回避反应的获得和保留没有影响。这些数据表明 Aβ 的组织病理学效应存在偏侧性，并且单次注射的效应部分是短暂的。这些发现还表明，阿尔茨海默病中的斑块和缠结形成之间存在直接关联，并支持使用该大鼠模型来筛选可能改变与阿尔茨海默病相关的初始病理事件的药物，这些病理事件发生在广泛的行为障碍表现变得明显之前。
To examine the time course of the histopathological effects of bilateral injections of amyloid-β 25-35 (Aβ) and to determine if these effects are associated with a reduction in choline acetyltransferase activity and behavioral impairments, we injected Aβ (5.0 nmol) into the amygdala of young male Fischer rats. Control rats received vehicle infusions. For histological analysis, animals were sacrificed at 8, 32, 64, 96, and 128 days postoperatively (n = 21–33 per timepoint). Aβ induced neuronal tau-2 staining in the right, but not the left amygdala and hippocampus. Aβ also induced reactive astrocytosis and neuronal shrinkage within the right hippocampus and amygdala, respectively. As with tau-2, these same brain regions within the left hemisphere in the Aβ-treated rats were significantly less affected. In addition, Aβ appeared to induce microglial and neuronal interleukin-1β staining. The histopathological effects of Aβ peaked at 32 days postoperatively but were not associated with a reduction in amygdaloid choline acetyltransferase activity. In a separate experiment, behavioral effects of bilateral intra-amygdaloid injections of Aβ were analyzed at 34–52 days postoperatively. In an open field test, the treatment groups differed only in the numbers of rears emitted (p = 0.016). There was no effect of Aβ in the Morris water maze or in the acquisition and retention of a one-way conditioned avoidance response. These data suggest a laterality in the histopathological effects of Aβ and that the effects of single injections are in part transient. These findings also suggest a direct association between plaque and tangle formation in Alzheimer’s disease, and support the use of this rat model to screen drugs that may alter the initial pathological events associated with Alzheimer’s disease, that occur before the manifestations of extensive behavioral impairments become evident.
影响因子：
64.8
作者：
GOATE, A;CHARTIERHARLIN, MC;HARDY, J
通讯作者：
HARDY, J