The World Health Organization predicts that depressive disorders will be the greatest contributor to the global burden of disease by 2030. Major depression is thought to comprise a heterogeneous group of diseases caused by genetic, epigenetic and environmental factors. In humans, detrimental early life events, such as maternal neglect or abuse during childhood, are associated with increased risk of emotional disorders including major depression that may persist into adulthood. In fact, experimental and clinical studies have shown that the immaturity and plasticity of the central nervous system during childhood make it particular sensitive to stress at a young age, which may cause significant and permanent changes in brain structure and function.
On the other hand, recent clinical and experimental data suggest that the pathophysiology of several neuropsychiatric disorders, including depressive syndromes, involves activation of the immune system in response to inflammatory agents. In fact, pro-inflammatory cytokines alter tryptophan metabolism, affecting the activity of serotonin, a neurotransmitter with a key role in the modulation of mood. Therefore, the tryptophan metabolic route becomes imbalanced during depression, enhancing an alternative metabolic pathway, the kynurenine synthesis pathway, and decreasing the availability of tryptophan to be metabolized into serotonin. This metabolic change has been directly associated to the development of depressive symptoms in humans and in experimental animal models.
In a recent study published in Progress in Neuro-Psychopharmacology & Biological Psychiatry, we have shown that maternal separation indeed induces both neuroinflammation and long-lasting emotional alterations in mice. The study was developed during Irene Gracia-Rubio’s PhD training at the GReNeC and done in collaboration with other research teams: the group led by Roser Nadal in UAB for maternal behaviour evaluation, and also with Oscar Pozo and Josep Marcos, researchers of the Neuroscience Program at IMIM (Hospital del Mar Research Institute) for the analysis of the kynurenine pathways. To have the opportunity to work with all these researchers in a collaborative project has been a very positive experience.
Our aim was to explore the interplay between depressive symptoms in behavioural models, neuroinflammation, and alterations in the tryptophan-kynurenine pathway since these mechanisms could lead to the discovery of new therapy approaches.
For that, we set up different behavioural models to induce conditions of early life adversity in male and female mice. Although most studies are done only in males, we decided to study female mice since the risk of suffering depression is double in women than in men.
We used two conditions: the maternal separation paradigm in mice as a model of early life neglect, and the standard rearing condition (the ‘control’), in which offspring remained with their mothers for 21 days. We then looked at the effect of both conditions on emotional behaviour during adolescence and into adulthood.
To test these effects, we performed a range of tests of anxiety, depressive symptoms and other emotional-related behaviours. To test anxiety, we used the elevated plus maze, a test that evaluates the capability of a rodent to explore new and stressful environments. Anxiety-like behaviour is reflected by an attenuated exploratory behaviour in mice. For testing depressive-like symptoms, we used the tail-suspension test, a model to evaluate despair behaviour, in this case, the time spent immobile when a mouse is confronted to an inescapable stressful situation.
At the physiological level, we looked for signs of neuroinflammation in different brain areas, and analysed metabolites of the tryptophan-kynurenine pathway to explore the link between depressive symptoms and inflammatory reactions.
Our results showed that adverse events during early life in mice increase risk of long-lasting emotional alterations during adolescence and into adulthood. These emotional disturbances were particularly severe in females. Behavioural impairments, including depressive symptoms, were associated with neuroinflammatory reactions in the two brain regions evaluated (prefrontal cortex and hippocampus).
In conclusion, these findings support the preeminent role of neuroinflammation in emotional disorders. Our results lead us to propose that detrimental early life events such as maternal neglect reproduce most of the behavioural alterations associated with depressive symptoms in mice. These alterations seem to be long lasting since adult mice also showed these emotional alterations. We also found that females were more sensitive to adverse conditions than males since the detrimental effects observed were more intense and persisted longer in time in female mice. Our study also supports the notion that the imbalance of the tryptophan-kynurenine metabolism and the association of neuroinflammatory reactions underlie these emotional impairments under our experimental conditions.
Future investigations will explore the influence of maternal separation and neuroinflammation in other psychiatric disorders, in particular psychotic and drug use disorders.
Gracia-Rubio I, Moscoso-Castro M, Pozo OJ, Marcos J, Nadal R, Valverde O. Maternal separation induces neuroinflammation and long-lasting emotional alterations in mice. Prog Neuropsychopharmacol Biol Psychiatry. 65: 104-17, 2016. DOI: 10.1016/j.pnpbp.2015.09.003.
Cedric Notredame, a group leader at the CRG, tells us in his “Slow bioinformatics blog” his personal and interesting story behind the development of T-coffee, a method for multiple sequence alignment which he developed during his PhD and which is currently widely used.
“For those who have no clue what T-Coffee does, it is a multiple sequence aligner. It means that it takes a bunch of biological sequences – typically proteins – that have evolved from a common ancestor by accumulating mutations, insertions and deletions…”
If you want to know the real story behind the T-coffee success, read Notredame’s blog here!
The World Antibiotic Awareness Week took place last 14-20 November, and the Antibiotic Resistance Initiative ISGlobal team took the chance to explain to the world what are the main difficulties on the fight against antibiotic resistance – a serious problem that threatens our ability to treat infectious diseases and poses a serious risk to the progress made in global health in the past decades. They summarise the issues in four battlefronts:
1- New antibiotics
3- Mechanisms of antibiotic resistance
You can read the whole report here.
The González lab at the Institute of Evolutionary Biology (CSIC-UPF), which focuses on understanding how organisms adapt to the environment, is seeking a lab technician to join their research team. You can read more about this position – with a starting date around February 2017 – here.
You can read a bit about the lab’s citizen science project “Melanogaster: Catch the fly!” in this post.
And here you can see a post about a recent publication of the lab where they discovered several naturally occurring independent transposable element insertions in the promoter region of a cold-stress response gene in the fruitfly Drosophila melanogaster.
Ribosome profiling is a sequencing technique that detects regions in mRNAs that are being translated. Using this technique, researchers have observed mysterious patterns of translation in many transcripts believed to be non-coding (lncRNAs, or long non-coding RNAs). The patterns are very similar to those observed in protein-coding genes but the translated proteins are generally smaller. Aside from their sequence, we know nothing about these peptides. Are they functional? Do they reflect some background noise of the translation machinery?
Núria López-Bigas started her lab on Computational Oncogenomics at the GRIB, within the PRBB, ten years ago. After a very successful decade, we are sad to see her leaving. We wish her all the best in her lab’s new adventure, and we hope the very fruitful interactions she has started with the different groups at the park will continue to prosper.
In her last post on her blog, Núria says thanks to the GRIB, the UPF, the PRBB community and the PRBB Intervals programme… We want to say, thanks to you Núria, for the great research you have done and for being such an open, collaborative and supportive person, both within the scientific community at the park and with outreach events for the general public! You will be missed. Good luck and see you soon!
Guillaume Filion’s latest post is aimed at those wanting to understand the details of how the Burrows–Wheeler transform (an algorithm used in data compression) works. It may be of particular interest to those genomics researchers working on alignments, since, Filion says, the Burrows-Wheeler indexing is used to perform the seeding step of the DNA alignment problem, and it’s exceptionally well adapted to indexing the human genome.
For those of you who are not afraid of the small mathematical details, you can see this “The grand locus” post here.
In this recent post by the HealthISglobal blog, Margarita Triguero, a PhD student at CREAL (now part of ISGLobal), gives us an overview about some recent studies showing the effects of natural spaces – mostly green spaces, both big and small – on health. As she says, blue spaces, such as lakes, rivers, or the sea, have been much less studied so far, but that’s about to change with a new international project called “BlueHealth Project“, which is led from the UK and in which the CREAL/ISGlobal researchers are involved.
Looking forward to hear more about this new project, which started earlier this year and will run until 2020! For the time being, you can read Margarita’s post here!
Post written by Toni Hermoso, bioinformatician at the CRG.
It’s been almost a decade since the term “Open Science” first appeared in Wikipedia. The page was created by Aaron Swartz and initially redirected to the “Open Access” entry. Some years later this young activist committed suicide as a result of the pressure from the judicial charges against him after having uploaded many privative licensed articles to the Internet.
Parallel to these events, Creative Commons licenses, a set of recommendations intended to foster sharing in the digital world, became increasingly popular, and many novel publishing initiatives took advantage of them for promoting open access to scientific literature.
At the same time, more and more government agencies started to demand that the benefactors of their funding should provide their publication results openly within a certain period of time. So, if research was not published originally in an open-access journal (golden road) it should be eventually uploaded in an institutional repository (green road). Furthermore, preprints, an already common practice in Physical Sciences, started to become widespread in Biosciences after the creation of portals such as BioRxiv.
However, despite the bloom of Open-Access (OA) journals and the introduction of a more favouring legislation, there are still strong concerns regarding the future of open access in science. This is mostly due to the fact that the publishing sector is effectively controlled by very few parties, which often provide pay walled content. A reaction to this situation is evidenced by initiatives such as Sci-Hub, which is defiantly providing free-access to those restricted articles.
In any case, there is more to Open Science than Open Access. We could highlight at least two other major facets: Open Data and Open Methodology. These are the indispensable two pilars for making reproducibility in modern science actually possible. In general terms, they may be the initial and raw data (straight from machines or sensors) or the final outcomes such as chart images or spreadsheets. The recent data flood has made necessary the birth of established public open repositories (e.g. Sequence Read Archive or the European Variant Archive) so researchers could freely reuse and review existing material.
It is also a common requirement from these repositories that data must be available in an open format, so other researchers may process them with different tools or versions than the ones originally used. This latter aspect is intimately associated to Open Source, which is also essential for ensuring a reproducible methodology. As a consequence, an increasing number of journals are requiring submitters to provide both data and program code so reviewers may assess by themselves that results are those that are claimed to be.
The present challenge is how to transfer those good practices -which originated in the software engineering world and later permeated into computational sciences- to the wide scientific community, where subject systems may be far less controllable (e.g., organisms or population samples). In order to help on this, there is an increasing effort in training scientists on technologies such as control version systems (e.g. GitHub), wikis or digital lab notebooks. All these kind of systems can enable collaboration of several different parties in an open and traceable way.
Even though there are some practices in everyday scientific activity, such as peer review, that are still under experimentation within the open umbrella, hopefully we may expect that in the future more and more of the key points we commented above will be just taken for granted. At that stage we might not even need to distinguish Open Science from simply SCIENCE anymore.
Citizen Science is blooming. There’s a growing number of examples of research projects in which the general population can participate. In this post at the blog Health ISGlobal, the researcher Irene Eleta (CREAL) talks about some of these projects which are related to air pollution and that scientists at CREAL /ISGlobal are leading, such as CITI-SENSE.