Could autism stem from epigenetic changes before birth?

A new study suggests that cases of idiopathic autism—that is, autism with no known cause—may stem from epigenetic abnormalities detectable early in fetal development. Epigenetic changes are changes that alter the effects of DNA by turning genes “on” or “off” without changing the DNA sequence. 

Chia-Wen Lin and colleagues hypothesized that a common cause could underlie the various types of immune dysregulation seen in autism, including inflammation of the brain and gut. To explore this theory, the researchers studied BTBR mice, which are used as a mouse model of autism. They focused on the hematopoietic cells from which immune cells are derived, as well as on the yolk sac and the aorta-gonad-mesonephros (AGM), which are involved in the process of creating hematopoietic cells. 

The researchers found that dysregulation of epigenetic machinery mediated by an enzyme called HDAC1 altered the development of “progenitor” cells that later develop into the yolk sac and AGM and impacted the development of immune cells called microglia. “Subsequently,” they say, “these changes result in the dysregulation of the immune system, leading to gut dysbiosis and hyperactive microglia in the brain.” In addition, the researchers found that administering inhibitors of HDAC1 suppressed inflammation and microglial activation. 

The researchers also found that dysregulated immunity in the mice led to specific profiles of gut dysbiosis. This, they say, could aid in the categorization of autism caused by immune dysregulation. 

They conclude, “[I]t is clear that the abnormalities in the brain and peripheral organs (such as the intestines) seen in autism are caused by epigenetic abnormalities in the hematopoietic stem cell lineage, the ancestor of immune cells.”

Citations

“A common epigenetic mechanism across different cellular origins underlies systemic immune dysregulation in an idiopathic autism mouse model,” Chia-Wen Lin, Dian E. Septyaningtrias, Hsu-Wen Chao, Mikiko Konda, Koji Atarashi, Kozue Takeshita, Kota Tamada, Jun Nomura, Yohei Sasagawa, Kaori Tanaka, Itoshi Nikaido, Kenya Honda, Thomas J. McHugh, and Toru Takumi, Molecular Psychiatry, May 2022 (online). Address: Toru Takumi, Department of Physiology and Cell Biology, Kobe University School of Medicine, Chuo, Kobe, 650-0017, Japan, [email protected]. 

—and— 

“Does autism begin in the womb?”, news release, Kobe University, May 2, 202