Mice expressing the A53T mutant form of human alpha-synuclein exhibit hyperactivity and reduced anxiety-like behavior.
Mice expressing the A53T mutant form of human alpha-synuclein exhibit hyperactivity and reduced anxiety-like behavior.
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DOI：
10.1002/jnr.22331
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发表时间：
2010-06
影响因子：
4.2
通讯作者：
Sidhu, Anita
中科院分区：
文献类型：
--
作者：
Graham, Dianca R.;Sidhu, Anita
与α-突触核蛋白（α-Syn）相关的基因突变与帕金森病（PD）的发病机制有关。PD主要是一种运动障碍，但已知患者会经历焦虑和其他情绪障碍。在这项研究中，我们研究了hA 53 T突变在发展过程中的影响，通过分析去甲肾上腺素（NET），血清素（SERT）和多巴胺（DAT）转运蛋白的蛋白表达，除了评估运动和焦虑样行为。我们观察到与正常和年轻小鼠相比，转基因动物在8个月时DAT表达显著降低。我们使用高架十字迷宫、旷场试验和旋转棒装置来评估2、8和12月龄的野生型和hA 53 T半合子小鼠。我们的研究结果表明，12个月大的转基因小鼠花更多的时间在开放的武器，并显示了更多的高架十字迷宫开放条目与野生型对照组和年轻的小鼠相比。旷场测试结果表明，12个月大的小鼠比野生型或年轻小鼠在整体上旅行更远，并且在内部区域旅行更多。转棒测试表明，8个月和12个月大的转基因小鼠比野生型对照小鼠或更年轻的小鼠表现更好。总体而言，8-12个月大的转基因小鼠表现出焦虑样行为减少和多动增加的趋势。这些结果表明A53 T α-Syn突变在PD小鼠模型中的焦虑样和多动行为中可能起作用，表明这些行为可能与该疾病共病。
Genetic mutations associated with α-synuclein (α-Syn) are implicated in the pathogenesis of Parkinson’s disease (PD). PD is primarily a movement disorder, but patients are known to experience anxiety and other mood disorders. In this study, we examined the effect of the hA53T mutation during development by analyzing the protein expression of norepinephrine (NET), serotonin (SERT), and dopamine (DAT) transporters in addition to assessing locomotor and anxiety-like behavior. We observed significant decreases in DAT expression at 8 months in transgenic animals compared with normal and younger mice. We used the elevated plus maze, open-field test, and rotarod apparatus to evaluate wild-type and hA53T hemizygous mice at 2, 8, and 12 months of age. Our results showed that 12-month-old transgenic mice spend more time in the open arms and display a greater number of open entries of the elevated plus maze compared with wild-type controls and younger mice. Open-field test results showed that 12-month-old mice travel a greater distance overall and travel more in the inner zone than either wild-type or younger mice. Rotarod testing showed that 8- and 12-month-old transgenic mice perform better than either wild-type controls or younger mice. Overall, 8–12-month-old transgenic mice showed a trend toward reduced anxiety-like behavior and increased hyperactivity. These results indicate a possible role of the A53T α-Syn mutation in anxiety-like and hyperactive behaviors in a PD mouse model, suggesting that these behaviors might be comorbid with this disease.
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影响因子：
16.2
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