Maternal infection during pregnancy increases the risk for psychiatric disorders in the child, but the path between the two is something of a mystery. In a study published in Biological Psychiatry, senior author use a mouse model to show that activation of the mother's immune system may cause long-term alterations in the programming of the offspring's genome, known as epigenetic modifications, which lead to behavioral abnormalities in adulthood.
"This study suggests that immunologic activation may be the connection between maternal infection to epigenetic changes that produce lasting changes in brain development," said Editor of Biological Psychiatry.
The findings provide new insight into the molecular mechanisms behind the risk factor. The alterations were found in a specific type of epigenetic modification called DNA methylation, which has been increasingly implicated in the origin of neurodevelopmental disorders. Altered DNA methylation appeared throughout the offspring's genome, and differed based on the timing of infection.
Researchers induced a viral-like infection in pregnant mouse mothers at two important time points during brain development of the offspring, in early and late gestation. Immune activation at both time points produced alterations in a few common genes associated with neurodevelopment, but most were distinct.
For example, late prenatal infection altered methylation of genes related to the development and function of GABA cells, whereas earlier exposure disrupted genes important for Wnt signaling, a pathway fundamental to early developmental events during embryogenesis. The findings indicate the importance of the timing of prenatal immune activation, and suggest that earlier infection may lead to more serious effects on neurodevelopment.
"Another intriguing finding of our study is that the pattern of DNA methylation in prenatally infected offspring changes over time," said the author, noting that alterations that were present when the mice reached adulthood were not observed when the mice were born. According to the author, the findings suggest that the modifications are dynamic and are likely influenced by activity-dependent events as the mice age.
"The adult emergence of multiple epigenetic modifications also raises the clinically relevant question as to whether some of these anomalies could be attenuated or even prevented by early interventions targeting the epigenetic machinery," said the author.
This would have important implications because the researchers found that the infection-induced modifications had functional consequences. The mRNA levels of genes showing differential methylation were altered in the offspring, indicating the epigenetic changes were modulating gene expression.
Further, the offspring exhibited cognitive and behavioral abnormalities present in animal models of neurodevelopmental disorders, such as schizophrenia and autism, suggesting that prenatal infection may cause genome-wide methylation abnormalities in these disorders. Thus, the possibility of targeting these modifications could open a potential avenue for preventative treatments in people exposed to prenatal infection.
https://www.elsevier.com/about/press-releases/research-and-journals/prenatal-infection-may-alter-brain-development-via-epigenetic-changes
http://www.biologicalpsychiatryjournal.com/article/S0006-3223(16)32671-3/abstract
Latest News
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Other Top Stories
Genetics links high blood pressure and obesity to reduced lifespan
Read more
A gene mutation enhances cognitive flexibility in mice
Read more
Inherited origin of prostate cancer in families
Read more
A gene mutation either slows or accelerates ALS
Read more
Genetic processes that determine short-sightedness
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Selenium, diabetes, and the…
By newseditor
Posted 23 Apr
Long-term neuropsychologica…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar