Functional Genomic Analyses Identify Pathways Dysregulated in Animal Model of Autism.
Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders that display complicated behavioral symptoms.



Using gene expressing profiling and the weighted gene co-expression network analysis (WGCNA), we studied genes coregulated by similar factors such as genetic variants or environmental effects in the hippocampus in an animal model of autism.



From microarray data, we identified 21,388 robustly expressed genes of which 721 genes were found to be differently expressed in the valproic acid-treated group compared to the control group. WGCNA identified multiple co-expression modules known to associate with cognitive function, inflammation, synaptic, and positive regulation of protein kinase activating. Many of these modules, however, have not been previously linked to autism spectrum disorders which included G-protein signaling, immunity, and neuroactive ligand-receptor interaction pathway. The downregulation of the highly connected (hub) genes Taar7h and Taar7b in neuroactive ligand-receptor interaction pathway was validated by qRT-PCR. Immunoblotting and immunohistochemistry further showed that TAAR7 expression was downregulated not only in valproic acid-treated animals, but also BTBR T+tf/J mice.



This study highlights the advantages of gene microarrays to uncover co-expression modules associated with autism and suggests that Taars and related gene regulation networks may play a significant role in autism.
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Ji-Yun
JY
Huang
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Yun
Y
Tian
The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Hui-Juan
HJ
Wang
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Hong
H
Shen
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Huan
H
Wang
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.|Department of Pharmacy, Hangzhou No. 7 People's Hospital, Hangzhou, Zhejiang, China.
Sen
S
Long
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Mei-Hua
MH
Liao
Department of Neurology, School of Medicine, Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
Zhi-Rong
ZR
Liu
Department of Pharmacy, Hangzhou No. 7 People's Hospital, Hangzhou, Zhejiang, China.
Ze-Ming
ZM
Wang
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Dan
D
Li
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Rong-Rong
RR
Tao
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Tian-Tian
TT
Cui
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Shigeki
S
Moriguchi
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Kohji
K
Fukunaga
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China. changhuahan@zju.edu.cn.
Feng
F
Han
School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, China. lufx@zju.edu.cn.
Ying-Mei
YM
Lu
D000818:Animals; D000831:Animals, Newborn; D001321:Autistic Disorder / Q000150:complications / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D004777:Environment; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D063990:Gene Ontology; D053263:Gene Regulatory Networks / Q000187:drug effects; D023281:Genomics; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D014635:Valproic Acid / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014635:Valproic Acid
Autism; Gene; Microarray; Neuroactive ligand-receptor interaction pathway; Taar; VPA; WGCNA