In a recent paper entitled “Maternal valproic acid exposure leads to neurogenesis defects and autism-like behaviors in non-human primates” published in Translational Psychiatry (https://doi.org/10.1038/s41398-019-0608-1), a collaborative research team consisting of multiple laboratories established a novel drug-induced animal model of autism by revealing the effects of VPA on neural development and behavior in the offspring of non-human primates.
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 minority of patients have been associated with a clear genetic cause. What environmental factors cause and how they cause autism is a major question in the field of autism research. Taking antiepileptic drugs such as valproic acid (VPA) during pregnancy increases the risk of cognitive impairment and autism in children, but it is not clear how the antiepileptic drugs affect brain development and function.
Corresponding author Yong Q. Zhang, from the Institute of Genetic and Developmental Biology (IGDB), Chinese Academy of Sciences (CAS), said, "VPA treated rats during pregnancy are widely used models for autism research. However, there are apparent differences between rodents and humans in brain anatomy and behavioral characteristics, which limit the translational value of rodent models. Therefore, it is necessary to develop a non-human primate autism model to facilitate the translation of research results."
Four laboratories including Yong O. Zhang's team at IGDB, Huihui Zhou's team from the Shenzhen Institutes of Advanced Technology of CAS, professor Xiao-jiang Li's team from Jinan university, and professor Yong-hui Jiang from Duke university school of medicine worked closely on the project. They 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 VPA-exposed monkey offspring paid more attention to non-social information. These findings provide 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.
The research was funded by the Chinese Academy of Sciences, the Ministry of Science and Technology and the National Natural Science foundation of China.
Contact:
Qi Lei
Institute of Genetic and Developmental Biology, Chinese Academy of Sciences
Email: lqi@genetics.ac.cn
