Maussion Gilles, Moalic Jean-Marie, Simonneau Michel, Gorwood Philip, Ramoz Nicolas
INSERM U894, Centre de Psychiatrie et Neurosciences (CPN), Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France.
INSERM U894, Centre de Psychiatrie et Neurosciences (CPN), Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France.
Behav Brain Res. 2019 Feb 1;359:903-909. doi: 10.1016/j.bbr.2018.06.023. Epub 2018 Jun 21.
Autistic spectrum disorders (ASDs) are neurodevelopmental disorders for which genetic components have been well defined. However, specific gene deregulations related to synapse function in the autistic brain have not been as extensively described. Based on a candidate genes approach, we present in this study the expression data of 4 transcripts of interest (BDNF, CAMK2a, NR-CAM and RIMS1) located at the synapse in two regions of interest in the context of the ASDs; the lobule VI of cerebellum and the Brodmann area 46. We have also genotyped in our cohort the coding single nucleotide polymorphism rs6265, located in the BDNF gene. After correction for age and sex, whereas no change was observed in the lobule VI between controls and autistic patients, we found a significant increase of BDNF expression level in the BA46 from autistic patients. No significant interaction between the rs6265 genotype and autism was observed for the BDNF expression. However, "A" allele carriers are more likely to have increased BDNF levels. Finally, we found a significant positive correlation between BDNF and RIMS1 expression levels. Our data suggest that these two molecules which are involved in cell signalling at the synapse, might have coordinated expressions and, that BDNF regulation in the brain has to be investigated further in the context of ASDs.
自闭症谱系障碍（ASD）是一类神经发育障碍，其遗传成分已得到明确界定。然而，与自闭症大脑中突触功能相关的特定基因失调尚未得到广泛描述。基于候选基因方法，我们在本研究中呈现了位于突触处的4个感兴趣转录本（BDNF、CAMK2a、NR-CAM和RIMS1）在自闭症谱系障碍背景下两个感兴趣区域（小脑小叶VI和布罗德曼46区）的表达数据。我们还对队列中位于BDNF基因的编码单核苷酸多态性rs6265进行了基因分型。在校正年龄和性别后，虽然在小脑小叶VI中未观察到对照组与自闭症患者之间有变化，但我们发现自闭症患者BA46区中BDNF表达水平显著升高。对于BDNF表达，未观察到rs6265基因型与自闭症之间存在显著相互作用。然而，携带“A”等位基因的个体更有可能BDNF水平升高。最后，我们发现BDNF与RIMS1表达水平之间存在显著正相关。我们的数据表明，这两种参与突触细胞信号传导的分子可能具有协同表达，并且在自闭症谱系障碍背景下，大脑中BDNF的调节有待进一步研究。
