Open AccessDownregulation of the Expression of Mitochondrial Electron Transport Complex Genes in Autism Brains
Author(s) -
Anitha Ayyappan,
Nakamura Kazuhiko,
Thanseem Ismail,
Matsuzaki Hideo,
Miyachi Taishi,
Tsujii Masatsugu,
Iwata Yasuhide,
Suzuki Katsuaki,
Sugiyama Toshiro,
Mori Norio
Publication year - 2013
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12002
Subject(s) - autism , downregulation and upregulation , gene , gene silencing , biology , gene expression , neuroscience , genetics , psychology , psychiatry
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 A utism T issue P rogram, USA . Q uantitative 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 C omplex III and C omplex IV , and seven genes of C omplex V showed brain region‐specific reduced expression in autism. ATP5A1 ( C omplex V ), ATP5G3 ( C omplex V ) and NDUFA5 ( C omplex 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.