Different susceptibility to neurodegeneration of dorsal and ventral hippocampal dentate gyrus: a study with transgenic mice overexpressing GSK3β.
Different susceptibility to neurodegeneration of dorsal and ventral hippocampal dentate gyrus: a study with transgenic mice overexpressing GSK3β.
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DOI：
10.1371/journal.pone.0027262
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Hernández F
中科院分区：
文献类型：
--
作者：
Fuster-Matanzo A;Llorens-Martín M;de Barreda EG;Ávila J;Hernández F
背侧海马区参与记忆和学习过程，而腹侧区域与情绪和焦虑过程有关。海马依赖性记忆和行为改变并不总是同时出现在神经退行性疾病中。在这项研究中，我们已经测试了这一假设，背侧和腹侧齿状回（DG）区域以不同的方式响应增加的糖原合成酶激酶3β（GSK 3 β）转基因小鼠，神经变性的遗传模型。反应性星形胶质细胞增多表明背侧DG的组织应力，而腹侧区域没有显示该标记。这些变化发生与总细胞数显着减少，并与一个显着较高的水平，在背侧区比腹侧的细胞死亡，如测量的fractin阳性细胞。生物化学分析显示，与背侧区相比，海马腹侧区中的酶的那些残基中磷酸化的GSK 3 β水平更高，这表明所观察到的易感性部分是由于不同的GSK 3调节。以前用这种动物模型进行的研究已经证明了Morris水迷宫和物体识别测试中的损伤，指出背侧海马萎缩。在这里，我们表明，用于评估情绪状态的两个测试，即明暗箱和新奇抑制喂养测试，表明GSK 3 β小鼠没有表现出任何焦虑相关的障碍。因此，我们的研究结果表明，在体内过表达GSK 3 β导致背侧而不是腹侧海马DG神经变性，并表明这两个地区并没有表现出类似的方式在神经变性过程中。
Dorsal hippocampal regions are involved in memory and learning processes, while ventral areas are related to emotional and anxiety processes. Hippocampal dependent memory and behaviour alterations do not always come out in neurodegenerative diseases at the same time. In this study we have tested the hypothesis that dorsal and ventral dentate gyrus (DG) regions respond in a different manner to increased glycogen synthase kinase-3β (GSK3β) levels in GSK3β transgenic mice, a genetic model of neurodegeneration. Reactive astrocytosis indicate tissue stress in dorsal DG, while ventral area does not show that marker. These changes occurred with a significant reduction of total cell number and with a significantly higher level of cell death in dorsal area than in ventral one as measured by fractin-positive cells. Biochemistry analysis showed higher levels of phosphorylated GSK3β in those residues that inactivate the enzyme in hippocampal ventral areas compared with dorsal area suggesting that the observed susceptibility is in part due to different GSK3 regulation. Previous studies carried out with this animal model had demonstrated impairment in Morris Water Maze and Object recognition tests point out to dorsal hippocampal atrophy. Here, we show that two tests used to evaluate emotional status, the light–dark box and the novelty suppressed feeding test, suggest that GSK3β mice do not show any anxiety-related disorder. Thus, our results demonstrate that in vivo overexpression of GSK3β results in dorsal but not ventral hippocampal DG neurodegeneration and suggest that both areas do not behave in a similar manner in neurodegenerative processes.
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影响因子：
16.2
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