An international research team established a novel drug-induced animal model of autism by revealing the effects of valproic acid (VPA) on neural development and behavior in the offspring of non-human primates. Their findings were published in
Translational Psychiatry.
Children with autism spectrum disorder (ASD) exhibit behavioral characteristics such as social communication deficits, restricted and repetitive behaviors. Epidemiological studies show that about 1% of children show autism, but only a few have a clear genetic cause.
What and how the environmental factors cause autism is a major scientific problem in the field of autism research. Administration of antiepileptic drugs such as VPA during pregnancy increases the risk of cognitive impairment and autism in children, but it is not clear how antiepileptic drugs affect brain development and function.
"VPA treated rats during pregnancy are a widely used model in autism research. However, there are significant differences between rodents and humans in brain anatomy and behavioral characteristics, which greatly hinder the translational value of rodent models. Therefore, it is necessary to develop a corresponding non-human primate autism model to facilitate the clinical translation of research results," said Dr. ZHANG Yongqing, the corresponding author of the research from the Institute of Genetic and Developmental Biology (IGDB) of the Chinese Academy of Sciences (CAS).
ZHANG's team, in collaboration with ZHOU Huihui's team from the Shenzhen Institutes of Advanced Technology under CAS, Prof. LI Xiaojiang's team from Jinan University and Prof. JIANG Yonghui from Duke University, obtained 2 full-term aborted fetuses and 5 surviving crab-eating monkey offspring after intraperitoneal injection of VPA sodium on the 26th and 29th days of pregnancy.
The aborted fetuses showed neurogenesis defects in a dose dependent manner. In addition, the offspring of the VPA treated monkeys showed social deficits and stereotyped behaviors. Eye tracking analysis showed that the exposed monkey offspring paid more attention to non-social information.
These findings provide more direct experimental evidence for the increased risk of autism in children whose mother takes VPA during pregnancy. Developmental deficits in the brain and behavioral abnormalities support VPA-treated monkeys as an effective animal model for autism, providing a new model system for further study.
The research was supported by the Chinese Academy of Sciences, the Ministry of Science and Technology and the National Natural Science Foundation of China.
