IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation.
IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation.
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DOI：
10.1186/1742-2094-8-52
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发表时间：
2011-05-19
影响因子：
9.3
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Wei H;Zou H;Sheikh AM;Malik M;Dobkin C;Brown WT;Li X
虽然自闭症的发病机制尚不清楚，但越来越多的研究表明，中枢神经系统（CNS）的局部炎症可能有助于自闭症的发展。近年来的研究表明，IL-6在中枢神经系统的发育和可塑性中具有重要作用。采用免疫组织化学方法检测各组大鼠小脑中IL-6的表达。采用腺病毒载体转染的方法在体外培养的小脑颗粒细胞中过表达IL-6。细胞粘附和迁移实验、DiI标记、TO-PRO-3染色和免疫荧光分别检测细胞粘附和迁移、树突棘形态、细胞凋亡和突触蛋白表达。在这项研究中，我们发现IL-6在自闭症患者的小脑中显著增加。我们通过用IL-6病毒表达载体转染培养的小鼠小脑颗粒细胞来研究IL-6如何影响神经细胞的发育和功能。我们证明，IL-6在颗粒细胞中的过度表达引起颗粒细胞粘附和迁移的损伤，但对树突棘的形成或颗粒细胞凋亡的影响不大。然而，IL-6过表达刺激颗粒细胞兴奋性突触的形成，而不影响抑制性突触。我们的研究结果提供了进一步的证据，异常IL-6可能与自闭症。此外，我们的研究结果表明，自闭症患者大脑中升高的IL-6可以改变神经细胞的粘附，迁移，并导致兴奋和抑制回路的失衡。因此，IL-6表达增加可能是自闭症发病机制的部分原因。
Although the cellular mechanisms responsible for the pathogenesis of autism are not understood, a growing number of studies have suggested that localized inflammation of the central nervous system (CNS) may contribute to the development of autism. Recent evidence shows that IL-6 has a crucial role in the development and plasticity of CNS. Immunohistochemistry studies were employed to detect the IL-6 expression in the cerebellum of study subjects. In vitro adenoviral gene delivery approach was used to over-express IL-6 in cultured cerebellar granule cells. Cell adhesion and migration assays, DiI labeling, TO-PRO-3 staining and immunofluorescence were used to examine cell adhesion and migration, dendritic spine morphology, cell apoptosis and synaptic protein expression respectively. In this study, we found that IL-6 was significantly increased in the cerebellum of autistic subjects. We investigated how IL-6 affects neural cell development and function by transfecting cultured mouse cerebellar granule cells with an IL-6 viral expression vector. We demonstrated that IL-6 over-expression in granule cells caused impairments in granule cell adhesion and migration but had little effect on the formation of dendritic spines or granule cell apoptosis. However, IL-6 over-expression stimulated the formation of granule cell excitatory synapses, without affecting inhibitory synapses. Our results provide further evidence that aberrant IL-6 may be associated with autism. In addition, our results suggest that the elevated IL-6 in the autistic brain could alter neural cell adhesion, migration and also cause an imbalance of excitatory and inhibitory circuits. Thus, increased IL-6 expression may be partially responsible for the pathogenesis of autism.
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影响因子：
30.8
作者：
Durand, Christelle M.;Betancur, Catalina;Bourgeron, Thomas
通讯作者：
Bourgeron, Thomas
影响因子：
6.2
作者：
Bozdagi O;Sakurai T;Papapetrou D;Wang X;Dickstein DL;Takahashi N;Kajiwara Y;Yang M;Katz AM;Scattoni ML;Harris MJ;Saxena R;Silverman JL;Crawley JN;Zhou Q;Hof PR;Buxbaum JD
通讯作者：
Buxbaum JD
DOI：
10.1016/j.ijdevneu.2010.06.006
发表时间：
2010-10-01
影响因子：
1.8
作者：
Jiang, Qian;Wu, Ye;Jiang, Yuwu
通讯作者：
Jiang, Yuwu
影响因子：
3.8
作者：
Chez, Michael G.;Dowling, Tim;Kominsky, Matt
通讯作者：
Kominsky, Matt
影响因子：
3.3
作者：
Ashwood, P;Wakefield, AJ
通讯作者：
Wakefield, AJ