Exposure to a compound used to treat migraines and seizures causes characteristics associated with autism, groundbreaking research with zebrafish has demonstrated.
Source: Oregon State University
The study, conducted by the Oregon State University and Wenzhou Medical University, showed how valproic acid exposure resulted in phenotypes and behaviours consistent with the autism spectrum disorder (ASD), validating the zebrafish as a model for studying ASD and its causes.
Autism spectrum disorder consists of five related neurodevelopmental disorders characterized by pervasive impairments in social interactions, deficits in verbal and nonverbal communication, repetitive patterns of behaviors and unusual sensitivity to sensory stimulation. All of the factors behind autism are not known, but the etiology is known to have both genetic and environmental components, including prenatal exposure to two drugs: thalidomide, a sedative associated with severe birth defects, and valproic acid.
As to the results of the study, developmental effects observed at teratogenic concentrations included malformations and macrocephalic phenotypes, whilst non-teratogenic concentrations showed behaviours relatable to those of autism spectrum disorder, including hyperactive movement behaviour and deficient social behaviour. Phenotypic analysis also showed significant increased neural stem cell proliferation, which would explain as potential mechanism of inducing the physical and behavioural changes by the VPA.
All in all, these results are consistent with human characteristics and have been replicated in rodent models, positioning the zebrafish as alternative model for studying ASD.
Journal Reference:
- Jiangfei Chen, Lei Lei, Linjie Tian, Fei Hou, Courtney Roper, Xiaoqing Ge, Yuxin Zhao, Yuanhong Chen, Qiaoxiang Dong, Robert L. Tanguay, Changjiang Huang. Developmental and behavioral alterations in zebrafish embryonically exposed to valproic acid (VPA): An aquatic model for autism. Neurotoxicology and Teratology, 2018; 66: 8 DOI: 10.1016/j.ntt.2018.01.002