Department of Psychiatry, Osmania Medical College, Hyderabad, India.
PLoS One. 2011 May 9;6(5):e19488. doi: 10.1371/journal.pone.0019488.
Several children with autism show regression in language and social development while maintaining normal motor milestones. A clear period of normal development followed by regression and subsequent improvement with treatment, suggests a multifactorial etiology. The role of inflammation in autism is now a major area of study. Viral and bacterial infections, hypoxia, or medication could affect both foetus and infant. These stressors could upregulate transcription factors like nuclear factor kappa B (NF-κB), a master switch for many genes including some implicated in autism like tumor necrosis factor (TNF). On this hypothesis, it was proposed to determine NF-κB in children with autism.
Peripheral blood samples of 67 children with autism and 29 control children were evaluated for NF-κB using electrophoretic mobility shift assay (EMSA). A phosphor imaging technique was used to quantify values. The fold increase over the control sample was calculated and statistical analysis was carried out using SPSS 15.
We have noted significant increase in NF-κB DNA binding activity in peripheral blood samples of children with autism. When the fold increase of NF-κB in cases (n = 67) was compared with that of controls (n = 29), there was a significant difference (3.14 vs. 1.40, respectively; p<0.02).
This finding has immense value in understanding many of the known biochemical changes reported in autism. As NF-κB is a response to stressors of several kinds and a master switch for many genes, autism may then arise at least in part from an NF-κB pathway gone awry.
一些自闭症儿童在语言和社交发展方面出现退化，同时保持正常的运动里程碑。正常发展之后出现退化，随后经过治疗有所改善，这表明自闭症是由多种因素引起的。炎症在自闭症中的作用现在是一个主要的研究领域。病毒和细菌感染、缺氧或药物治疗都可能影响胎儿和婴儿。这些压力源可能会上调核因子 kappa B（NF-κB）等转录因子，NF-κB 是许多基因的主要开关，包括一些与自闭症有关的基因，如肿瘤坏死因子（TNF）。基于这一假设，我们提出了检测自闭症儿童 NF-κB 的方案。
采用电泳迁移率变动分析（EMSA）法检测 67 例自闭症儿童和 29 例对照儿童外周血 NF-κB。采用磷光成像技术对其值进行定量。计算相对于对照样本的倍数增加，并使用 SPSS 15 进行统计分析。
我们注意到自闭症儿童外周血样本中 NF-κB DNA 结合活性显著增加。将病例组（n = 67）的 NF-κB 倍数增加与对照组（n = 29）进行比较，差异具有统计学意义（分别为 3.14 和 1.40；p<0.02）。
这一发现对于理解自闭症中许多已知的生化变化具有重要价值。由于 NF-κB 是对多种压力源的反应，也是许多基因的主要开关，因此自闭症至少部分可能是由于 NF-κB 途径异常引起的。
