Downregulation of the Expression of Mitochondrial Electron Transport Complex Genes in Autism Brains

被引：82

作者：

Anitha, Ayyappan ^{[1
]}

Nakamura, Kazuhiko ^{[2
]}

Thanseem, Ismail ^{[2
]}

Matsuzaki, Hideo ^{[1
]}

Miyachi, Taishi ^{[1
]}

Tsujii, Masatsugu ^{[1
,4
]}

Iwata, Yasuhide ^{[2
]}

Suzuki, Katsuaki ^{[1
]}

Sugiyama, Toshiro ^{[3
]}

Mori, Norio ^{[1
,2
]}

机构：

[1] Hamamatsu Univ Sch Med, Res Ctr Child Mental Dev, Hamamatsu, Shizuoka 4313192, Japan

[2] Hamamatsu Univ Sch Med, Dept Psychiat & Neurol, Hamamatsu, Shizuoka 4313192, Japan

[3] Hamamatsu Univ Sch Med, Dept Child & Adolescent Psychiat, Hamamatsu, Shizuoka 4313192, Japan

[4] Chukyo Univ, Fac Sociol, Toyota, Japan

来源：

BRAIN PATHOLOGY | 2013年 / 23卷 / 03期

关键词：

autism; electron transport complex; mitochondria; post-mortem brain; INCREASED OXIDATIVE STRESS; ANTERIOR CINGULATE CORTEX; SPECTRUM DISORDERS; ENERGY-METABOLISM; PROPIONIC-ACID; DYSFUNCTION; CHILDREN; MODEL; VOLUME; CHAIN;

D O I：

10.1111/bpa.12002

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Mitochondrial dysfunction (MtD) and abnormal brain bioenergetics have been implicated in autism, suggesting possible candidate genes in the electron transport chain (ETC). We compared the expression of 84 ETC genes in the post-mortem brains of autism patients and controls. Brain tissues from the anterior cingulate gyrus, motor cortex, and thalamus of autism patients (n=8) and controls (n=10) were obtained from Autism Tissue Program, USA. Quantitative real-time PCR arrays were used to quantify gene expression. We observed reduced expression of several ETC genes in autism brains compared to controls. Eleven genes of Complex I, five genes each of Complex III and Complex IV, and seven genes of Complex V showed brain region-specific reduced expression in autism. ATP5A1 (Complex V), ATP5G3 (Complex V) and NDUFA5 (Complex I) showed consistently reduced expression in all the brain regions of autism patients. Upon silencing ATP5A1, the expression of mitogen-activated protein kinase 13 (MAPK13), a p38 MAPK responsive to stress stimuli, was upregulated in HEK 293 cells. This could have been induced by oxidative stress due to impaired ATP synthesis. We report new candidate genes involved in abnormal brain bioenergetics in autism, supporting the hypothesis that mitochondria, critical for neurodevelopment, may play a role in autism.

引用

页码：294 / 302

页数：9

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