Drug abuse and emotional disorders, such as anxiety and depression, are generating a serious social problem. This is why Rafael Maldonado’s neuropharmacology group at the CEXS-UPF studies the common biological mechanisms involved in these two phenomena. They focus particularly in nicotine, cannabis, cocaine and ecstasy, and in the possible mechanisms underlying the abusive consume of these substances.
Maldonado explains there are three factors to understand why some people become addictive and others don’t: drug consume (the quantity, the frequency, the mode); social and environmental factors; and individual vulnerability, which includes genetic factors. A classical example of the effect of the environment is how the American marines that were heroin addicts in Vietnam quitted easily once back at home.
In order to understand addiction and emotional disorders, the group, formed by 29 people, uses different techniques: classical pharmacological strategies, using compounds that act on the nervous system receptors; ‘knock-out’ mice in which a specific gene has been deleted in order to understand its function; and animal models for behaviour studies which, according to Maldonado, are very complex but once they are established they allow a good prediction of what can happen in humans.
Maldonado highlights the discovery that specific components of the endogenous opioid system are a common substrate for different addictive behaviours as a major contribution of his group. His dream: that this knowledge gives rise to effective treatments for the addicts, who are people with a chronic disease, emphasizes the researcher.
This article was published in the El·lipse publication of the PRBB.
What is a virus?
We used to think we knew. Before we discovered giant viruses, size was central to the definition of a virus: 0.3 micrometer filters were used to isolate microorganisms, and anything smaller than that which was infectious, was a virus.
So giant viruses were a bit of a surprise?
We discovered them by mistake. No biologist studying viruses could have discovered them, because the first thing they did was to discard anything that wasn’t filtered. We were working on intracellular parasitic bacteria when a 10-year old water sample arrived at our laboratory. It was thought to have been the cause of a pneumonia outbreak, but nobody had yet been able to isolate the microorganism responsible. Someone at our lab had the idea to use electron microscopy and there it was! It was infecting an amoeba but it didn’t look like a bacterium, although it was really big.
How big are giant viruses?
They can be 30 times bigger than the average virus, up to 750 nm. You can even see them with a light microscope! And their genome is larger than that of many bacteria. When we sequenced the mimivirus we were also surprised to see it was genetically very complex. It has 1018 genes, including many related to translation. These are not supposed to be present in viruses, since viruses use the host machinery to translate their genome into proteins.
That must have been a shock.
It was revolutionary, and it raised a lot of questions. With such complexity, could we still say that viruses are not alive? Recently researchers have found the first virus that can be infected by another virus – I say, if you can get sick, you are very definitely alive!
How do giant viruses change our view of evolution?
They are very old and the genomic analysis of marine viruses shows that they are very common and probably major players in the ecology. Although they are different from other viruses, if one analyses their evolutionary relationships, giant viruses fit perfectly with other viruses. However, they also have things in common with bacteria, such as the structure of the capsid, as well as with eukaryotes.
They are a real mix then?
My controversial theory is that DNA was invented by viruses to protect themselves from their host, an RNA cell. Slowly, the cell took that DNA machinery and incorporated it, and the nucleus was formed. At the same time, the viruses started to lose some of those genes that the cell had incorporated. After several cycles of infection, the cell gradually increased its complexity and the viruses reduced their genome.
Have we seen it all?
I think we will find bigger viruses, with more translation genes. One day we will have a real problem defining a virus!
The May 2012 edition of the PRBB newspaper, El.lipse, a monthly bilingual newspaper, is now available: http://bit.ly/KprWYh
Is working at night harmful? This is one of the issues that the group of Manolis Kogevines (CREAL) is addressing in its research as explained in the new issue of El·lipse. You could also learn about the cutting-edge work with cord blood stem cells for transplants by Nadim Mahumd from the University of Illinois. The genetic origin of Afghanistan’s ethnic groups, the results of the most ambitious genetic study so far about osteoporosis and a European map of mental disorders are among the news that can be discovered in this month’s newspaper. But you could also learn about the book exchange initiative at the PRBB and also how to make a delicious aubergines “a la parmigiana” meal. Don’t miss it!
The New Cajal Era
More than 100 years have passed after the first contributions made by Santiago Ramón y Cajal to the neural network theory. Nowadays neuroscientists take advantage of innovative tools to study neural circuits in order to understand complex behaviours.
This image by David D’Amico, from the group on neurobehavioral phenotyping of mouse models of disease at the CRG, shows the hippocampus of a transgenic mouse expressing yellow fluorescent protein (YFP) in specific subsets of central neurons. This type of tansgenic mice help scientists to understand neural networks in both physiological and pathological conditions.
An interview published in Ellipse, the monthly magazine of the PRBB.
Philippe Grandjean, Adjunct Professor of Environmental Health at Harvard University, delivered a lecture in Barcelona invited by Jordi Sunyer, from the CREAL, a ‘model institution’ according to Grandjean. Sunyer introduced the talk about what the Danish-born scientist calls a ‘silent pandemic’: the effect of chemical pollutants on neurodevelopment.
To what extent do in utero conditions affect adult health?
There are several studies that show that exposing pregnant women to mercury can affect the development of their children, even if they are not affected themselves. Minamata disease, a neurological syndrome caused in children whose mothers suffer severe mercury exposure, was discovered in Japan in the 1950s, and was a shock to the world. Since then many other studies have demonstrated the effect of mercury exposure on foetal development. However, it wasn’t until 2009 that an international agreement was reached to control mercury emissions into the environment!
How many pollutants can be neurotoxic during early development?
There are about 100,000 chemicals in the world. About 200 have been documented as being neurotoxic to adult humans, and only five to foetuses: lead, mercury, PCBs (polychlorinated biphenyls), arsenic and toluene. However, the foetal brain is much more sensitive than the adult one! So I think we are only seeing the tip of the iceberg. For example, many pesticides can be neurotoxic to humans, as the nervous system of the insects that the pesticides attack is very similar to ours. For example, we did a study in Ecuador on pregnant women working in flower plantations, who were exposed to pesticides. Their children at school age presented a delay of up to two years in their brain development.
Are these effects irreversible?
The brain has great plasticity, so one might think that with enough effort we could get kids with lower cognitive abilities to catch up with the rest. But the problem is for this plasticity to occur your neurones must be in the right place. You cannot develop your full potential if you don’t have the correct anatomical foundation and if your nerve cells and connections are abnormal.
And does mercury exposure cause anatomical problems in the brain?
Normally we have no way of checking, but with Minamata disease, quite a few of the children died, and when they were examined at autopsy it was seen that their brain cells appeared in a disrupted pattern, as if their migration during brain development had been affected. So yes, we think so.
If they are so dangerous, why are these pollutants not banned?
The problem is that chemicals are not banned unless it’s proven that they are dangerous. But then it’s too late! I think we need to move towards the opposite strategy: a chemical should be banned unless it is proven not to be dangerous to brain development. Prevention should come before science. After all, we have only once chance to develop a brain.