Brain region-specific decrease in the activity and expression of protein kinase A in the frontal cortex of regressive autism.
Brain region-specific decrease in the activity and expression of protein kinase A in the frontal cortex of regressive autism.
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DOI：
10.1371/journal.pone.0023751
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Chauhan A
中科院分区：
文献类型：
--
作者：
Ji L;Chauhan V;Flory MJ;Chauhan A
自闭症是一种严重的神经发育障碍，其特征是语言、沟通和社交技能受损。在退行性自闭症中，受影响的儿童最初表现出正常的社交和语言发展的迹象，但最终失去这些技能并发展为自闭症行为。蛋白激酶在g蛋白偶联、受体介导的信号转导中是必不可少的，并参与神经元功能、基因表达、记忆和细胞分化。我们研究了退行性自闭症患者脑额叶、颞叶、顶叶、枕叶皮层和小脑的死后脑组织样本中蛋白激酶A（一种环amp依赖性蛋白激酶）的活性和表达；无临床退行史的自闭症受试者；以及同龄发育正常的对照对象。与对照组和非退行性自闭症个体相比，退行性自闭症个体额叶皮层PKA活性和PKA催化亚基PKA （C-α）的表达显著降低。在退行性自闭症患者的小脑、颞叶、顶叶和枕叶皮层中没有观察到这种变化。此外，PKA活性和PKA （C-α）的表达在非退行性自闭症组与对照组之间无显著差异。这些结果表明，自闭症的消退可能部分与pka介导的蛋白磷酸化减少和细胞信号异常有关。
Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In regressive autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA), a cyclic AMP–dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with regressive autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-α), a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with regressive autism compared to control subjects and individuals with non-regressive autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with regressive autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-α) between non-regressive autism and control groups. These results suggest that regression in autism may be associated, in part, with decreased PKA-mediated phosphorylation of proteins and abnormalities in cellular signaling.
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DOI：
10.1111/j.1749-6632.1990.tb16893.x
发表时间：
1990-10-15
影响因子：
5.2
作者：
ANDERSON, GM;HORNE, WC;COHEN, DJ
通讯作者：
COHEN, DJ
DOI：
10.1073/pnas.1834280100
发表时间：
2003-09-02
影响因子：
11.1
作者：
Bourtchouladze, R;Lidge, R;Tully, T
通讯作者：
Tully, T
影响因子：
2.9
作者：
Cheh, Michelle A.;Millonig, James H.;Wagner, George C.
通讯作者：
Wagner, George C.
影响因子：
3.5
作者：
Deogracias, R;Espliguero, G;Rodríguez-Peña, A
通讯作者：
Rodríguez-Peña, A
影响因子：
9.8
作者：
Benayed, R;Gharani, N;Millonig, JH
通讯作者：
Millonig, JH