Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York, NY 10314, USA.
Mediators Inflamm. 2011;2011:785265. doi: 10.1155/2011/785265. Epub 2011 Oct 20.
Autism is a neurodevelopmental disorder characterized by problems in communication, social skills, and repetitive behavior. Recent studies suggest that apoptotic and inflammatory mechanisms may contribute to the pathogenesis of this disorder. Nuclear factor-κB (NF-κB) is an important gene transcriptional factor involved in the mediation of inflammation and apoptosis. This study examined the activities of the NF-κB signaling pathway in the brain of autistic subjects and their age-matched controls. The NF-κB activation is also determined in the brain of BTBR mice, which is a promising animal model for study of pathogenic mechanisms responsible for autism. Our results showed that the level of IKKα kinase, which phosphorylates the inhibitory subunit IκBα, is significantly increased in the cerebellum of autistic subjects. However, the expression and phosphorylation of IκBα are not altered. In addition, our results demonstrated that the expression of NF-κB (p65), and the phosphorylation/activation of NF-κB (p65) at Ser536 are not significantly changed in the cerebellum and cortex of both autistic subjects and BTBR mice. Our findings suggest that the NF-κB signaling pathway is not disregulated in the brain of autistic subjects and thus may not be significantly involved in the processes of abnormal inflammatory responses suggested in autistic brain.
自闭症是一种神经发育障碍，其特征是在沟通、社交技能和重复行为方面存在问题。最近的研究表明，凋亡和炎症机制可能有助于这种疾病的发病机制。核因子-κB（NF-κB）是一种重要的基因转录因子，参与炎症和凋亡的调节。本研究检测了自闭症患者和年龄匹配对照组大脑中 NF-κB 信号通路的活性。还在 BTBR 小鼠的大脑中确定了 NF-κB 激活情况，BTBR 小鼠是研究自闭症发病机制的有前途的动物模型。我们的结果表明，磷酸化抑制亚基 IκBα 的 IKKα 激酶水平在自闭症患者的小脑显著升高。然而，IκBα 的表达和磷酸化没有改变。此外，我们的结果表明，NF-κB（p65）的表达以及小脑和皮质中 NF-κB（p65）在 Ser536 的磷酸化/激活在自闭症患者和 BTBR 小鼠中均无明显变化。我们的研究结果表明，NF-κB 信号通路在自闭症患者的大脑中没有失调，因此可能不会显著参与自闭症大脑中异常炎症反应的过程。
