Researchers find epigenetic tie to neuropsychiatric disorders

July 21, 2014
“Our work presents new leads to understanding neuropsychiatric disorders,” UCI's Emiliana Borrelli said.

Dysfunction in dopamine signaling profoundly changes the activity level of about 2,000 genes in the brain's prefrontal cortex and may be an underlying cause of certain complex neuropsychiatric disorders, such as schizophrenia, according to UC Irvine scientists.

This epigenetic alteration of in that receive this neurotransmitter showed for the first time that dopamine deficiencies can affect a variety of behavioral and regulated in the .

The study, led by Emiliana Borrelli, a UCI professor of microbiology & molecular genetics, appears online in the journal Molecular Psychiatry.

"Our work presents new leads to understanding neuropsychiatric disorders," Borrelli said. "Genes previously linked to schizophrenia seem to be dependent on the controlled release of dopamine at specific locations in the brain. Interestingly, this study shows that altered dopamine levels can modify gene activity through epigenetic mechanisms despite the absence of genetic mutations of the DNA."

Dopamine is a neurotransmitter that acts within certain brain circuitries to help manage functions ranging from movement to emotion. Changes in the dopaminergic system are correlated with cognitive, motor, hormonal and emotional impairment. Excesses in dopamine signaling, for example, have been identified as a trigger for neuropsychiatric disorder symptoms.

Borrelli and her team wanted to understand what would happen if dopamine signaling was hindered. To do this, they used mice that lacked in midbrain neurons, which radically affected regulated dopamine synthesis and release.

The researchers discovered that this receptor mutation profoundly altered gene expression in neurons receiving dopamine at distal sites in the brain, specifically in the prefrontal cortex. Borrelli said they observed a remarkable decrease in expression levels of some 2,000 genes in this area, coupled with a widespread increase in modifications of basic DNA proteins called histones – particularly those associated with reduced gene activity.

Borrelli further noted that the dopamine receptor-induced reprogramming led to psychotic-like behaviors in the mutant mice and that prolonged treatment with a dopamine activator restored regular signaling, pointing to one possible therapeutic approach.

The researchers are continuing their work to gain more insights into the genes altered by this dysfunctional dopamine signaling.

Explore further: Boost for dopamine packaging protects brain in Parkinson's model

Related Stories

Seeking the causes of hyperactivity

April 25, 2014

The 60 trillion cells that comprise our bodies communicate constantly. Information travels when chemical compounds released by some cells are received by receptors in the membrane of another cell. In a paper published in ...

Recommended for you

Elderly may face increased dementia risk after a disaster

October 24, 2016

Elderly people who were uprooted from damaged or destroyed homes and who lost touch with their neighbors after the 2011 tsunami in Japan were more likely to experience increased symptoms of dementia than those who were able ...

Research examines role of early-life stress in adult illness

October 24, 2016

Scientists have long known that chronic exposure to psychosocial stress early in life can lead to an increased vulnerability later in life to diseases linked to immune dysfunction and chronic inflammation, including arthritis, ...

Plan ahead for successful aging, researcher says

October 20, 2016

For many people, the prospect of aging is scary and uncomfortable, but Florida State University Assistant Professor Dawn Carr says that research reveals a few tips that can improve our chances of a long, healthy life.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.