Could a treatment for Parkinson's disease help the social impairment of diseases like autism?

September 2, 2013, University of Minho

A stressful pregnancy might be the last thing a future mother needs, but it is to her unborn baby that this stress spells real trouble. All because stress hormones (called glucocorticoids or GCs) can change foetal brain development, causing the new individuals to develop serious behavioural and/or emotional problems. Despite this danger we remain far from understanding how GCs work. But now a study in rats by a Portuguese team has discovered that the prenatal (before birth) effect of GCs on behaviour is linked to problems in dopamine (a brain messenger). Surprisingly, they also found that it is possible (and easy) to reverse the abnormal behaviours seen in these individuals, a discovery with possible implications for neurological diseases like autism and attention-deficit hyperactivity disorder (ADHD).

Sonia Borges and Barbara Coimbra from the University of Minho found that when rats are exposed to high levels of GCs during its foetal formation, not only they develop abnormal behaviour, but their are lower than normal in several brain areas linked to pleasure. Once normal levels are restored, though, the emotional and social abnormalities seen in these animals disappear. This seems to show that triggered by early life trauma could be reversed by dopamine, what is remarkable. The study, which is coming out September in the journal Neuropsychopharmacology, has implications for associated with dopamine and early neurodevelopmental problems, such as depression, anxiety, ADHD, schizophrenia and autism. Ana João Rodrigues, one of study leaders (together with Nuno Sousa) warns for the need to be very cautious though " Although there are some clues that prenatal stress may affect emotional and social behaviour in humans, our work is still at very early stages. All we can really say" – she points – "is that dopamine is able to improve deficiencies in social behaviour and this might have important implications for diseases characterised by social impairment".

GCs are crucial life hormones – if they mediate the negative effects of stress, they are also involved in all types of normal functions of the body; from controlling the immune system and regulate the metabolism to even help the maturation of foetal organs, GCs are indispensable for life. In fact, even if they can provoke problems in the foetal brain, these hormones are still routinely given to pregnant women in danger of premature delivery, to help foetal lung maturation. So it is urgent to understand better how GCs work to be able to make better crucial, even life-depending, decisions.

So in the study to be published Borges, Coimbra and colleagues looked at their effects before birth, by exposing rats still in the uterus to high levels of GCs (the equivalent of having a very stressed mother), and found that they went to develop signs of depression and lack of motivation (like reported before), but they also saw social impairments. Animals exposed to prenatal stress played less, had less "happy" calls ("happy" and "sad" calls can be differentiated by their sound frequencies) but also interacted awkwardly with others.

"Since our group had seen before that exposure to prenatal GCs affected a neural circuit important for the feelings of reward and pleasure (the mesolimbic system) " - explains Rodrigues - "and in juvenile rats rough tumble and play is one of the most rewarding behaviours, we wondered if the problem could be dopamine, a key molecule in this system."

And in fact, it was found that "prenatal stress" rats lacked dopamine in both the amygdala and the nucleus accumbens (NAc), which are regions of the mesolimbic system.  But what was remarkable was the next discovery – that L-dopa (a precursor of dopamine given to Parkinson's patients who also lack it) simply added to the water of the affected animals was enough to fully reverse their social and emotional abnormalities.

So the new study reveals that high GC levels/prenatal stress can lead to social impairments, as well as the emotional problems seen in previous studies, and this appears to result from reduced dopamine levels in linked to pleasure perception. And once these animals' dopamine levels are corrected the behavioural problems are also corrected.

So could things work similarly in humans?  In diseases like depression, autism and schizophrenia, which are characterised by emotional and social inadequacies and/or have already been linked to prenatal stress? Rodrigues alerts "To transfer these results to humans requires caution. These results do not mean that L-dopa is a miraculous drug to treat lack of motivation or depression, although it certainly appears that the mesolimbic dopamine system is critical in these problems. For now the most important thing is that we are starting to unveil GCs' induced molecular changes in specific neuronal circuits, which will help in the understanding of some of these problems".

Borges and Coimbra's study is interesting also because it finally "links the dots" – prenatal stress has already been associated to an increased incidence of several neurologic diseases and some of these to problems in . Social impairments like those seen autism and ADTH on the other hand are known to be more common in individuals that went through stressful prenatal periods. What the new study manages to reveal now is the "underneath story". And, of course, introduce the possibility of a treatment.

 But the work had one other interesting result: when the of the animals was being tested two rats exposed to prenatal stress put together didn't play but, surprisingly, the interaction of one of these and a normal animal had very different results. This because the normal individual would not rest inciting and provoking the "disturbed" rat to play until it finally started interacting. This supports the idea that interaction with other individuals can make a vital difference to revert the negative effects of pre-natal or early life stress on the brain, and should be encouraged as early as possible.

Explore further: Dopamine regulates the motivation to act

More information: Dopaminergic modulation of affective and social deficits induced by prenatal glucocorticoid exposure, Neuropsychopharmacology (September 2013) 38, 2068–2079; doi: 10.1038/ npp.2013.108

Related Stories

Dopamine regulates the motivation to act

April 29, 2013
The widespread belief that dopamine regulates pleasure could go down in history with the latest research results on the role of this neurotransmitter. Researchers have proved that it regulates motivation, causing individuals ...

Mother's touch could change effects of prenatal stress

October 16, 2012
Scientists at the Universities of Liverpool, Manchester, and Kings College, London, have found that mothers who stroke their baby's body in the first few weeks after birth may change the effects that stress during pregnancy ...

Does motherhood dampen cocaine's effects?

October 15, 2012
Mother rats respond much differently to cocaine than female rats that have never given birth, according to new University of Michigan research that looks at both behavior and brain chemistry.

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 ...

Dopamine not about pleasure (anymore)

December 3, 2012
(Medical Xpress)—To John Salamone, professor of psychology and longtime researcher of the brain chemical dopamine, scientific research can be very slow-moving.

Offspring of mothers stressed during pregnancy with a passive stress coping style more prone to obesity

July 30, 2013
Research to be presented at the Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior, shows that passively coping offspring ...

Recommended for you

Research reveals atomic-level changes in ALS-linked protein

January 18, 2018
For the first time, researchers have described atom-by-atom changes in a family of proteins linked to amyotrophic lateral sclerosis (ALS), a group of brain disorders known as frontotemporal dementia and degenerative diseases ...

Fragile X finding shows normal neurons that interact poorly

January 18, 2018
Neurons in mice afflicted with the genetic defect that causes Fragile X syndrome (FXS) appear similar to those in healthy mice, but these neurons fail to interact normally, resulting in the long-known cognitive impairments, ...

How your brain remembers what you had for dinner last night

January 17, 2018
Confirming earlier computational models, researchers at University of California San Diego and UC San Diego School of Medicine, with colleagues in Arizona and Louisiana, report that episodic memories are encoded in the hippocampus ...

Recording a thought's fleeting trip through the brain

January 17, 2018
University of California, Berkeley neuroscientists have tracked the progress of a thought through the brain, showing clearly how the prefrontal cortex at the front of the brain coordinates activity to help us act in response ...

Midbrain 'start neurons' control whether we walk or run

January 17, 2018
Locomotion comprises the most fundamental movements we perform. It is a complex sequence from initiating the first step, to stopping when we reach our goal. At the same time, locomotion is executed at different speeds to ...

Miles Davis is not Mozart: The brains of jazz and classical pianists work differently

January 16, 2018
Keith Jarret, world-famous jazz pianist, once answered in an interview when asked if he would ever be interested in doing a concert where he would play both jazz and classical music: "No, that's hilarious. [...] It's like ...


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.