A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Fall, 2016 | Number 4, Volume 30

Two studies offer clues about the role of epigenetic changes in autism spectrum disorders

Two new studies are shedding light on the relationship between autism spectrum disorders (ASD) and epigenetic changes. 

Epigenetic changes are alterations in gene activity that occur without changes to the DNA itself. These changes, which switch genes on or off, can sometimes be passed on to future generations. The causes of epigenetic changes are wide-ranging and include diet, chemical exposures, stress, disease processes, medications, and prenatal influences. 

In the first study, Wenjie Sun and colleagues examined post-mortem brain tissue samples from 45 individuals with ASD and 49 controls. They found that the samples from individuals with ASD exhibited a similar set of epigenetic changes, with more than 68% sharing a common pattern of histone acetylation (an epigenetic process that determines whether a gene is “hidden” or not) at 5,000 gene loci. The researchers say, “This suggests that, despite tremendous heterogeneity in the primary causes of autism, such as DNA mutations and environmental perturbations during development, ASD has molecular features that are commonly shared.” 

In the second study, Chang Soon Choi and colleagues injected pregnant mice with valproic acid, an anti-epileptic drug that can cause autistic-like symptoms in prenatally exposed animals and humans. The exposed male offspring exhibited autistic-like social impairments, abnormal marble-burying behavior, increased seizure susceptibility, hyperactivity, and decreased anxiety. When the researchers mated the exposed offspring with unexposed females to produce a second generation, and then mated second-generation males to unexposed females to create a third generation, the autistic-like behaviors found in the first generation persisted. In addition, the frontal cortices of first- and third-generation mice exhibited an imbalanced expression of excitatory and inhibitory synaptic markers. 

The researchers say, “These results open the idea that excitatory/inhibitory imbalance and ASD-like behavioral changes induced by environmental insults in mice can be epigenetically transmitted, at least to the third generation.” They add that their fi ndings “could help explain the unprecedented increase in ASD prevalence.”


Citations

“Histone acetylome-wide association study of autism spectrum disorder,” Wenjie Sun, Jeremie Poschmann, Ricardo Cruz-Herrera del Rosario, Jonathan Mill, Daniel H. Geschwind, Shyam Prabhaker, et al., Cell, Vol. 167, 1385-97, November 17, 2016 (free online). Address: Shyam Prabhakar at [email protected]

—and— 

“Shared epigenetic changes underlie different types of autism,” news release, Cell Press, November 2016. 

—and— 

“The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy,” Chang Soon Choi, Edson Luck Gonzalez, Ki Chan Kim, Sung Min Yang, Ji-Woon Kim, Darine Froy Mabunga, Jae Hoon Cheong, Seol-Heui Han, Geon Ho Bahn, and Chan Young Shin, Nature Scientific Reports, November 7, 2016 (free online). Address: Geon Ho Bahn, mompeian@ khu.ac.kr