Researchers find epigenetic tie to neuropsychiatric disorders

July 21, 2014, University of California, Irvine
“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

Boost for dopamine packaging protects brain in Parkinson's model

June 17, 2014
Researchers from Emory's Rollins School of Public Health discovered that an increase in the protein that helps store dopamine, a critical brain chemical, led to enhanced dopamine neurotransmission and protection from a Parkinson's ...

Deep brain stimulation for obsessive-compulsive disorder releases dopamine in the brain

April 30, 2014
Some have characterized dopamine as the elixir of pleasure because so many rewarding stimuli - food, drugs, sex, exercise - trigger its release in the brain. However, more than a decade of research indicates that when drug ...

Appetite accomplice: Ghrelin receptor alters dopamine signaling

January 25, 2012
New research reveals a fascinating and unexpected molecular partnership within the brain neurons that regulate appetite. The study, published by Cell Press in the January 26 issue of the journal Neuron, resolves a paradox ...

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 ...

Hunting down the trigger for Parkinson's: Failing dopamine pump damages brain cells

June 16, 2014
A study group at the Medical University of Vienna's Centre for Brain Research has investigated the function of an intracellular dopamine pump in Parkinson's patients compared to a healthy test group. It turned out that this ...

Long-term ADHD treatment increases brain dopamine transporter levels, may affect drug efficacy

May 15, 2013
Long-term treatment of attention deficit/hyperactivity disorder (ADHD) with certain stimulant medications may alter the density of the dopamine transporter, according to research published May 15 in the open access journal ...

Recommended for you

Intensive behavior therapy no better than conventional support in treating teenagers with antisocial behavior

January 19, 2018
Research led by UCL has found that intensive and costly multisystemic therapy is no better than conventional therapy in treating teenagers with moderate to severe antisocial behaviour.

Babies' babbling betters brains, language

January 18, 2018
Babies are adept at getting what they need - including an education. New research shows that babies organize mothers' verbal responses, which promotes more effective language instruction, and infant babbling is the key.

College branding makes beer more salient to underage students

January 18, 2018
In recent years, major beer companies have tried to capitalize on the salience of students' university affiliations, unveiling marketing campaigns and products—such as "fan cans," store displays, and billboard ads—that ...

Inherited IQ can increase in early childhood

January 18, 2018
When it comes to intelligence, environment and education matter – more than we think.

Modulating molecules: Study shows oxytocin helps the brain to modulate social signals

January 17, 2018
Between sights, sounds, smells and other senses, the brain is flooded with stimuli on a moment-to-moment basis. How can it sort through the flood of information to decide what is important and what can be relegated to the ...

Baby brains help infants figure it out before they try it out

January 17, 2018
Babies often amaze their parents when they seemingly learn new skills overnight—how to walk, for example. But their brains were probably prepping for those tasks long before their first steps occurred, according to researchers.

0 comments

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.