Altered serotonin, dopamine and norepinepherine levels in 15q duplication and Angelman syndrome mouse models.
Altered serotonin, dopamine and norepinepherine levels in 15q duplication and Angelman syndrome mouse models.
复制标题
DOI：
10.1371/journal.pone.0043030
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Reiter LT
中科院分区：
文献类型：
--
作者：
Farook MF;DeCuypere M;Hyland K;Takumi T;LeDoux MS;Reiter LT
儿童神经发育障碍，如Angelman综合征和自闭症，可能是神经元可塑性的潜在缺陷和突触信号持续问题的结果。其中一些缺陷可能是由于大脑不同区域的单胺水平异常造成的。UBE3A是一种基因，当母体缺失时会导致Angelman综合征(AS)，当母体复制时与自闭症相关。最近研究表明，UBE3A基因可以调节果蝇大脑中单胺的合成。因此，我们检测了Ube3a缺失和Ube3a重复动物的纹状体、腹侧中脑、额叶皮质、小脑皮质和海马单胺水平。我们发现5-羟色胺(5HT)是自闭症中的一种单胺类物质，在AS小鼠的纹状体和皮质中升高。在Ube3a缺失和Ube3a重复的动物中，与对照相比，纹状体、中脑和额叶皮质中的多巴胺水平几乎一致地升高，而不考虑Ube3a缺失和Ube3a重复的基因。根据之前发表的数据，在复制15q自闭症小鼠模型中，父系而不是母系的复制动物与它们的野生型后代相比，5HT水平下降。然而，母系复制动物在整个大脑中的5-羟色胺水平没有显著变化。这些异常的单胺水平可能是在AS和自闭症中观察到的许多行为异常的原因，但需要进一步的研究来确定这些变化中是否有任何纯粹依赖于大脑中的Ube3a水平。
Childhood neurodevelopmental disorders like Angelman syndrome and autism may be the result of underlying defects in neuronal plasticity and ongoing problems with synaptic signaling. Some of these defects may be due to abnormal monoamine levels in different regions of the brain. Ube3a, a gene that causes Angelman syndrome (AS) when maternally deleted and is associated with autism when maternally duplicated has recently been shown to regulate monoamine synthesis in the Drosophila brain. Therefore, we examined monoamine levels in striatum, ventral midbrain, frontal cerebral cortex, cerebellar cortex and hippocampus in Ube3a deficient and Ube3a duplication animals. We found that serotonin (5HT), a monoamine affected in autism, was elevated in the striatum and cortex of AS mice. Dopamine levels were almost uniformly elevated compared to control littermates in the striatum, midbrain and frontal cortex regardless of genotype in Ube3a deficient and Ube3a duplication animals. In the duplication 15q autism mouse model, paternal but not maternal duplication animals showed a decrease in 5HT levels when compared to their wild type littermates, in accordance with previously published data. However, maternal duplication animals show no significant changes in 5HT levels throughout the brain. These abnormal monoamine levels could be responsible for many of the behavioral abnormalities observed in both AS and autism, but further investigation is required to determine if any of these changes are purely dependent on Ube3a levels in the brain.
登录
查看更多内容
影响因子：
2.9
作者：
Allensworth, Melody;Saha, Anand;Heck, Detlef H.
通讯作者：
Heck, Detlef H.
影响因子：
3.6
作者：
Cook, Edwin H., Jr.;Leventhal, Bennett L.
通讯作者：
Leventhal, Bennett L.
影响因子：
6.1
作者：
Hogart A;Wu D;LaSalle JM;Schanen NC
通讯作者：
Schanen NC
影响因子：
56.9
作者：
Ansorge, MS;Zhou, MM;Gingrich, JA
通讯作者：
Gingrich, JA
影响因子：
25
作者：
通讯作者：
--