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Month: January 2013

Where does the energy come from that is needed as a carrier in neuron extensions?

Posted on by Priscille Rivière

The movement of molecules in the neuron extensions known as axons is a process that is vital for the survival of cells and the smooth operation of the nervous system. It is performed by vesicles that travel fast thanks to the energy-hungry molecular engines. At the “Signalling, neurobiology and cancer” Laboratory (Institut Curie/CNRS/Inserm) at the Institut Curie, the team headed by Frédéric Saudou[1], INSERM Director of Research, has shown that the vesicles have their own energy production system needed for travelling and do not depend on the mitochondria that are the main source of cell energy. This mechanism works by means of glycolysis, the first stage in the conversion of glucose and for the huntingtin protein, the protein that mutates in Huntington’s Disease, a neurodegenerative condition. The results were published on 31 January 2013 in the Cell journal.

Unlike carcinomas in which the cell proliferates, neurodegenerative conditions such as Alzheimer’s Disease, Parkinson’s Disease and Huntington’s Disease are due to the accelerated death of neurones. At the “Signalling, neurobiology and cancer” Laboratory (Institut Curie/CNRS/Inserm), part of the Institut Curie, the research team headed by Frédéric Saudou is studying the function of the huntingtin protein which mutates in Huntington’s Disease. “When it is altered, by a process that is still not fully understood, huntingtin causes the accelerated death of neurons in the striatum, the region of the brain in which Huntington’s disease first manifests” explains Frederic Saudou.

His team has shown the essential role played by huntingtin in the swift travel of vesicles through the neuron extensions or axons. axones. Huntingtin stimulates the progress of these vesicles by interacting with molecular engines, enabling them to travel to specific regions of the brain such as the striatum, the brain structure that is attacked in victims of Huntington’s Disease.

ATP, the engine essential for transporting the vesicles

So where does the cell energy come from that is vital for ensuring the transport of the vesicles in the axons over long distances, that may in some cases be as long as one metre? The adenosine triphosphate (ATP) molecule is an energy source shared by all animal and plant species. In humans, it is mostly produced by specialist organelles in the cells, known as the mitochondria. “In this project we have shown that a process other than the mitochondria is involved in the supply of energy to the molecular engines[1] responsible for movement along the axons” explains Frédéric Saudou. In fact, the inhibition of the mitochondrial function has no effect on this swift movement. On the other hand, the genetic inactivation of an enzyme that is essential for glycolysis, the first stage in the conversion of glucose into energy significantly reduces movement.

A mechanism that is dependent on the huntingtin protein

“The enzymes responsible for glycolysis are situated directly on the vesicle and produce the energy needed for the movement of the axons. We then tried to discover the mechanism responsible for fixing it on the vesicle membrane. Our researches have established that attachment to the vesicle is performed by the huntingtin protein. We do not yet know, however, whether this function is disrupted in Huntington’s disease” stresses Frédéric Saudou. Researchers do not exclude the existence, however, of other mechanisms that link the glycolysis enzymes to the vesicle membrane.

Image taken via microscopy showing the position of the vesicule of a glycolysis enzyme, the protein GAPDH (in red), with huntingtin (in green) shown in a neuron from a rat’s cortex. The vesicles have been coloured blue.

©Diana Zala/Institut Curie

More about Huntington’s Disease

Huntington’s Disease is a rare neurological disorder that affects one person in 10,000 and only manifests in adulthood. The most typical symptoms are mental disturbance (anxiety, irritability, depression), a progressive deterioration in intellectual capacity culminating in dementia, associated with abnormal involuntary jerking movements of the limbs, head and neck.

The genetic anomaly that causes Huntington’s disease is an abnormal increase in the repetition of the three nucleic acids (C, A and G – known as the CAG triplet) in the coding gene for the huntingtin protein. This results in an abnormal expansion of a repetition of an amino acid (polyglutamine or polyQ repetition) in the huntigtin protein. The mechanisms leading to the manifestation of the disease are still little understood and at present there is no treatment to prevent the emergence of symptoms inpatients. A better understanding of the cell processes that occur within the neurons should make it possible to identify new treatment strategies for this neuro-degenerative disease. Understanding these mechanisms could also help in the treatment of other conditions such as cancer.

[1] The molecular engines responsible for the movement of the molecule or cell structures throughout the cell skeleton are the proteins kinesin and dynein.

[1] Frédéric Saudou is head of the “Cell Signalling and Neurobiology” team in the Cell Signalling, Neurobiology and Cancer Unit at the Institut Curie/CNRS UMR 3306/Inserm U1005

First results of survey into relations between Inserm researchers and patient associations

Posted on by Priscille Rivière

Results to be unveiled during the 6th Inserm meeting with patient associations held at the French Senate

In conjunction with the Senate Commission for Social Affairs, Inserm has organised the 6th meeting between national research representatives and patient associations, to be held on Thursday, 31 January 2013. More than twenty researchers and association representatives will provide first-hand accounts and develop dialogue with the senators in front of more than 250 participants. During this event, the results of a large survey conducted on some 600 researchers from Inserm laboratories will be published to shed light on relations with patient associations. According to the results, 81% of researchers surveyed are in contact with patient associations, half of which are regular contacts. More than 400 different associations were cited by name. Two thirds of researchers in contact with an association consider the fact that “direct contact with patients provides additional motivation to research activities” to be “useful” or “determining”.

 


©fotolia

This year, the 6th National Research and Patient Association meeting aims to review and prepare the future prospects for a process that is gathering momentum: not only do relations between the world of research and patient associations exist, they are expanding and are actually involved in research progress, and, as a consequence progress in terms of the health of our fellow citizens. From now on these meetings will be used as a driving force for innovation and transformation in terms of relations between research and society at large.

The survey was a Gram1 initiative (think-tank with patient associations) and was conducted on Inserm researchers in 2012 to improve knowledge and understanding of the type of relations (and their mechanics) that researchers forge with associations and how they perceive this partnership. The first results will be presented during this meeting.

Six hundred and fifty researchers took part in this survey.


81% of them had contact with associations, half of which were ongoing. When asked to cite the name of the associations, more than 400 associations were cited by name (in addition to major associations with which everyone is familiar). Researchers who are also clinical practitioners are twice as likely to have relations with associations as their non-clinical colleagues.

The results show that researchers build up these relations over time. Relations increase in line with the researchers’ age and level of responsibility: 11% of researchers aged under 30 have ongoing relations with associations, 57% of researchers aged between 50-55 and 50% of 55-60 year olds.


In less than half of all cases, the researchers stated they received financial support. The amount over the total length of collaboration is extremely variable: lower than €40,000 in one out of four cases; and greater than €2,500,000 in 5% of cases. The researchers underlined the possibilities opened up by this support: seed-funding for projects and sponsorship of doctorates or post-doctorates. For their part, researchers support the associations in the field of scientific information for patients, outreach activities, participation in meetings and scientific monitoring. Researchers recognize the important role of scientific mediator, undertaken by associations for patients, meaning four out of five researchers agree with the following statement: “Patient associations are best placed to distribute information to the patients they represent”. 

When questioned on benefits in terms of progress in their research, half the researchers consider that information provided by the associations concerning the patients’ daily life and their expectations helps them in their research.


Beyond the support, financial or otherwise, provided for their projects, two thirds of researchers consider that working with a patient association provides a useful, or even determining, motivation for their activity, and 80% of them consider it enhances the value of research results.


In response to the statement: “Being involved in patient associations risks impeding researchers’ scientific freedom”, 70% of the researchers said they did not agree, and this figure rose to 77% for those with ongoing relations with an association. When asked whether “involvement with a patient association hinders their activity by taking up too much of their time”, more than half the researchers disagreed (this figure again rose to nearly two thirds for researchers with ongoing relations with an association).

The first results of Cairnet demonstrate that patient associations are present in the world of researchers, which goes against the image of researchers ‘cut-off’ in their laboratories.

The vast majority of researchers surveyed now consider patient associations not only as contacts but also as players who encourage their research activities. Clarification provided by the researchers themselves must make it possible to ensure even greater progress in these partnerships, which are supported by Gram at Inserm.

Inserm was supported by the Patient Association Think-tank (Gram) to organize this meeting. Chaired by Pr Syrota, Inserm CEO, Gram is composed of 20 members, half of which are representatives from patient associations, disabled persons or family members, and the other half is made up of Inserm researchers and managers. “It is a unique location for open exchanges and debates into all issues that link research activities, the resulting progress in knowledge and the persons likely to benefit” states Martine Bungener, Gram Chairwoman. 

La Fondation Bettencourt Schueller apporte un soutien de 1 675 000 € à la recherche biomédicale française

Posted on by Priscille Rivière

Le Human Brain Project gagne la compétition du plus grand fonds scientifique européen

Posted on by Priscille Rivière

OpenViBE2 : A major French project involving Brain-Computer Interfaces applied to video games

Posted on by Priscille Rivière

OpenViBE2 (2009-2013) is a collaborative research project, supported by finance from the ANR, that is based on the potential of the technologies known as “brain-computer interfaces”(ico) in the field of video games.This is a project that has brought together the scientific expertise needed through a multi-disciplinary consortium consisting of nine partners – the university laboratories who pioneered the field (INRIA, INSERM, cea, GIPSA-Lab), well-known video-game manufacturers (ubisoft, blacksheep studio, kylotonn games) and specialists in usage and transfer (lutin, clarte).After three years of work and achieving numerous scientific advances associated with the development of innovative industry prototypes, OpenViBE2 has made it possible to have greater control over the future of such technologies on the French market as well as internationally.

© Inserm / Hirsch, Philippe

  • Acting on thought thanks to brain-computer interfaces 

[break]A brain-computer interface enables users to send commands to a computer purely by using their mental activity. BCIs use electroencephalographic (EEG) devices based on electrodes that are placed on the surface of the head, and that record electrical signals corresponding to exchanges of electric current between the neurones. The electrical activity produced by the brain is then analysed in real time and translated into a command sent to the computer or any other automated system thus making it possible to move a cursor to the right or left, simply by mentally imaging the movements a hand would make.

Initiated in 2005 by INRIA and INSERM, the first OpenViBE (2005-2009) project, which was also supported by the ANR, was completed in 2009 with the creation of open-source software that made it possible to easily design, develop and test brain-computer interfaces (http://openvibe.inria.fr). Today, this is recognised software that is used throughout the world. The  OpenViBE2 software is a sequel to this initial project and is aimed at exploring these technologies more thoroughly by exploring them in a particularly complex applicational context –  that of video games. This is a relatively new field of application for BCIs. But the advent of low-cost EEG  helmets has opened the way to such applications.

The purpose of OpenViBE2 is thus to improve the current abilities of BCIs and test their use and their potential in the field of video games.

  • Video games: a growing market

[break]As a development of the “gesture-controlled” command (joystick, mouse, gamepad), the “mental” command is a new and very promising route in the field of video-gaming. Since the early 2000s, scientists have been tacking the scientific issue of how to incorporate BCI technologies to enable them to interact with virtual environments.

In this context, the aim of the OpenViBE2 project is to identify and use the gamer’s mental state and brain responses to interact with the game and/or adapt the actual content of the video game accordingly. A very original approach suggested in the project was to consider BCIs not as a substitution technique for the classic interfaces (joystick, mouse, gamepad) but rather to consider using the BCIs as a new way of playing that complements the traditional techniques. In this way, the gamer can continue to use a joystick while at the same time or at certain key moments in the game, he/she can also mobilise his/her brain activity for playing.

  • Advances in the Open ViBE2 project: promising innovations 

[break]Whether in respect of diseases and neurological syndromes, the world of entertainment or daily life, OpenViBE2 opens the way to innovative technologies and major interests for human beings. During the course of the OpenViBE2 project, major scientific advances have been obtained in these three fields:

In Neuroscience: identification of new mental activities linked to the attention processes.

In the first leg of the OpenViBE project, the  INSERM team known as “Mental Dynamics and Cognition (Dycog)” at the Lyon Neuroscience Research Centre (INSERM/CNRS) participated in the development of software capable of “writing through thought”, thus facilitating communication by people suffering from a motor handicap. OpenViBE2 offers new advances in the field of neurosciences that makes it possible to use interfaces brain-computer for therapeutic purposes in order to improve certain neurological disorders such as attention deficit disorders. Thanks to the device, researchers were able to analyse:

–   attention paid to the outside world by measuring in real time and selectively the level of engagement of the cerebral network responsible for seeking specific information in a visual scene.
–   attention paid by the user to an internal representation, c’est-à-dire i.e. the level of engagement of the cerebral network responsible for maintaining mental representation.
–    The level of distraction of a person by determining the real time in which a person is distracted and for how long.

The principle of virtual reality, used mainly in the serious game ADHD developed thanks to OpenViBE2, enabled researchers to obtain results with respect to attention deficit disorder. The virtual environment is similar to the real environment and the user has to concentrate in order to perform a task that he/she knows from the real world. This virtual training employs the process known as NeuroFeedback in which the user is required to self-regulate his/her mental activity.

“The serious game, which is associated with augmented reality, has a positive retraining effect that persists beyond the training session and into the real environment”, stresses Jean Philippe Lachaux, Director of Research at INSERM.



Progress is still necessary with respect to the device so that it can be accessible to all.

In processing signals: the CEA and GIPSA-Lab researchers have found new techniques to better filter and interpret electrical signals from the brain.

These make it possible in particular to eliminate noise interference (especially when it is linked to muscle activities such as facial muscles, blinking or jaw-clenching), and extracting the relevant brain activity as accurately and in as focused a manner as possible. These techniques are very useful in a gaming context, in which gamers may be very mobile.

In virtual reality and man-machine interaction: OpenViBE2 has enable the INRIA researchers to invent new concepts to interact with video games in the most original and effective way and suggest new world firsts:

–    The brain-computer “multi-player” interface: the INRIA researchers designed the very first  collaborative or competitive gaming application  in which the brain activities of two gamers were analysed simultaneously. Both players could play on the same side or in opposition to each other, in a simplified video football game.
–   The natural incorporation of BCI into the virtual world: researchers studied how to best incorporate the stimulation necessary for certain brain-computer interfaces based on  mental responses, by incorporating visual stimuli into the virtual world. For example, some BCIs “visual flashes” that are recognisable in the user’s brain. These can be incorporated into a video game, for example in the form of butterflies that beat their wings at different frequencies.
–   Automatic adaptation of the virtual world to the gamer’s mental state: Finally, researchers have offered radically new approaches in which elements of the virtual environment have been automatically modified depending on the player’s mental state. In a virtual maze game, guides are thus activated automatically if the user presents with too great a mental burden. This work has benefited internationally through the award of several science prizes (Best Paper Award, Eurohaptics 2012, BCI Award 2012 nominee).

  • The gaming room of the future

[break]The OpenViBE2 project has made it possible to develop numerous proofs of the academic concept and commercial video game prototypes all of them activated by the brain.

Video game manufacturers have worked directly with the INRIA university laboratories, as well as with INSERM, CEA and the GIPSA-Lab, to develop video games based on brain activity. This collaboration has made it possible to better define scientific research initiatives throughout the project and bring all the research together into solutions that are best suited to the technological constraints of the field of application.

During the course of the project, the partners introduced a huge campaign of experiments involving “brain-computer interfaces and video games” run by CHART  at the Cité des Sciences in the course of which nearly 400 testers tested the prototypes. The results of these experiments made it possible to highlight the attractions of these technologies to a wider public, and provide the consortium of partners with a large amount of user feedback. A standardisation project was also run by UBISOFT to define the “ideal” helmet best suited to the video-games market.

Here are a few examples of proofs of the concept developed by the university labs:

– MindShooter (INRIA): In this game, the gamer controls a spaceship shown at the bottom of the screen and he/she has to destroy the enemy ships at the top of the screen. Three commands are available: move right, move left, and fire. To activate them, the gamer must concentrate on the part of the ship that corresponds to the action he/she wishes to trigger.

– Brain Invaders (GIPSA-LAb): This game is inspired by the Japanese “Space Invaders” game. Once again, the aim is to destroy the spaceships on the screen, thanks to a mental response that is produced as soon as a rare but expected event occurs.

– Brain Arena (INRIA): This simplified “multi-player” football game enables two users to play together or one against the other using their mental powers.

Three commercial prototypes of video games based on mental activity have also been developed by the consortium.

– Cocoto Brain (Kylotonn Games): A “Casual game” based on mental activity, Entertainment for the Nintendo Wii console. The gamer needs to protect a fairy by preventing all her enemies from getting near her. The gamer has to concentrate on targets positioned over the enemies in order to neutralise them.

– BCI Training Center (Black Sheep Studio), a game of the “mental training” type using the EEG developed by Black Sheep Studio. The game enables the gamer to practice brain-training gaming activities (visual searching, finding a word in a grid) associated with a real-time adaptation of the game, depending on the player’s mental state measured by the EEG device (relaxation and concentration).

– A serious game for the treatment of attention deficit disorder (CLARTE): a prototype is designed for children destined for children suffering from attention deficit hyperactivity disorder (ADHD) has been developed by CLARTE. The virtual environment of this platform is a classroom in which the child suffering from ADHD is invited, for example, to watch a video on a screen in the class, of which the perceived quality is directly linked to his/her mental activity. Thus, if he/she wants to continue to watch the video under optimal conditions, he/she must continue to maintain his/her activity under the conditions indicated by the therapist. Several mini-games are also offered to improve his/her attentional ability using the EEG.

©Lachaux/Inserm

In conclusion, the OpenViBE2 project made it possible to acquire scientific expertise and technological know-how that is unique in the world, concerning the use of this very promising technology in a developing market. Important scientific advances have been obtained in many different fields, such as neuroscience, electrical signal processing from the brain, man-machine interfaces and virtual reality. The prototypes made it possible to illustrate numerous scientific results for the project in actual commercial settings.

The results of the project were capitalised in the form of know-how, methods and software such as the free OpenViBE software that ought to make it possible to have better future control over the opening up of these BCI technologies to the public at large. Discussions are currently taking place concerning the marketing of prototypes in the near future with help of the French start-up MENSIA TECHNOLOGIES.

More than 50 scientific papers have been presented at conferences or published in journals of reference.

Please find photographs to illustrate the project in the Inserm photothèque.

The skin aging regulator

Posted on by Priscille Rivière

 

Despite progress in regenerative medicine, with age, the skin loses its properties in an irreversible manner. The ATIP-Avenir team “Epidermal homeostasis and tumorigenesis” directed by Chloé Féral, an Inserm researcher at the French Cancer and Aging Research Institute (Inserm/CNRS/Université Sophia Antipolis), has just defined the cellular and molecular mechanisms involved in maintaining skin cells and skin healing in advanced years. These mechanisms, described in vivo in mice, engage molecule CD98hc, which is involved in epidermis renewal and could be an indicator of the skin’s capacity for regeneration.

The results were published in the Journal of Experimental Medicine review.

 

©Fotolia

The epidermis, the surface layer of the skin, is mainly composed of keratinocytes cells, which, in humans, are renewed continuously over a 21-day cycle. These cells are located on a membrane made up of components from the extracellular matrix that provides the junction with the dermis, the deep layer of the skin (see diagram).  The epidermis is renewed by cell proliferation and differentiation that maintains the balance of adult tissues. This balance, known as “homeostasis”, is essential for tissues to function correctly and any alterations to it are responsible for the physical changes associated with aging: sagging skin due to reduced skin cell proliferation, wound healing defects, loss of hair, etc.

The ATIP-Avenir team “Epidermal homeostasis and tumorigenesis” directed by Inserm researcher Chloé Féral, studied the numerous cellular factors involved in maintaining this balance. Particular attention was paid to CD98hc, a molecule known for its interaction with receptors that cause skin aging. With age, the activity of the transporter CD98hc and integrins (the receptors connected to the components in the extra cellular matrix) is disturbed. However, until now the mechanisms involved had never been identified.

Through their work, the researchers showed in vivo in mice that removing the gene CD98hc (coding gene for transporter CD98hc) disturbs skin balance and the healing process. By modifying cell proliferation and migration, removing this gene also causes a fault in the hair follicle cycle. The researchers have deciphered all the complex mechanisms associated with CD98hc, particularly integrin deregulation caused by this missing molecule in vivo. They confirm what was described in vitro: the amino acid transporter CD98hc modules the integrin signal, which is essential for skin renewal. As such, CD98hc actively participates in skin renewal through the efficient and widespread recruitment of skin cells when needed (healing a wound, for example).

“CD98hc appears to be necessary for rapid and effective skin renewal. Its reduced expression, observed in vivo in elderly mice, confirms its role in maintaining tissues, the hair follicle cycle and healing, which are disturbed with age,” states Chloé Féral. “The status of carrier CD98hc in vivo could be an indicator of the skin’s capacity to renew itself” she concludes.

© I-STEM

Skin renewal is driven by stem keratinocytes. The latter have two properties: active division and differentiation. Each keratinocyte produces two identical daughter cells. One remains static and divides again, whereas the other migrates to the upper layer, the differentiation layer, where it will provide the different types of skin cellls.

Inauguration of TherA-Image, imaging technology-assisted treatment platform

Posted on by Priscille Rivière

When research, medicine and high tech work together in Rennes

Imagine, in this hybrid operating theatre, surgeons, physicians and engineers surrounded by control screens, using enhanced and roboticised reality systems, enabling interventions that are even more accurate and safe. At the Signal and Image Processing Laboratory (University of Rennes 1 / Inserm), researchers, engineers and doctors at the Rennes CHU Cardio-pneumological Centre have been working together to bring the TherA-Image platform into existence.

They have designed and implemented interventional cardiology and mini-invasive surgery techniques, using image-guidance and computer-assistance through the TherA-Image platform. These procedures are designed to reduce to a minimum the time taken for the intervention and trauma from the operation. This means that the frailest patients will be able to have access to these innovative medical techniques that are designed to improve post-operative and the prognosis thanks to instruments and skills that are unique in Europe.

TherA-Image is a hybrid operating theatre, used for both patient care and de research in the field of health technology. It is a medico-technical platform located at the interface between the Rennes University Hospital, the University of Rennes 1, INSERM and the medical industry. It is here that computerised approaches are devised and deployed for planning interventions, assistance with operating procedures and assessment of these procedures.

TherA-Image possesses state-od-the-art imaging equipment (3D intra-operating observation, enhanced reality, cardiac electrophysiology), operating assistance (endovascular navigation and a catheterisation robot) as well as video broadcasting (to obtain remote expertise, provide training, etc.)


Treating cardiac insufficiency through resynchronisation therapy /©L. Després

This combination of equipment and skills in the same operating theatre in Rennes is unique in Europe. It is the result of a convergence of views that originated long ago in the LTSI multidisciplinary teams, that included doctors, researchers and engineers, and a solid partnership has been formed for the long-term, including industry leaders in their own field of interest.


©Replacing the thoracic aorta

Today, TherA-Image makes it possible to explore new approaches to cardiovascular treatment, in order to:

  • Treat cardiac insufficiency, especially through the type of treatment known as cardiac resynchronisation. Patients sometimes present with defects in the synchronisation of the heart ventricles. This means that the chambers of the heart do not all contract at the same time, so the heart no longer works efficiently and the patient becomes out of breath when making the slightest effort. Thanks to the TherA-Image platform, doctors and researchers can optimise the techniques and the implantable devices for electrically stimulating the heart.
  • Eliminate the sources of electrical disturbances inside the heart muscle that are the cause of cardiac dysrhythmia. Techniques and intra-corporeal navigation models have been developed for this purpose, as well as diagrams of the electrical current inside the heart muscle. The aim is to identify the sources of electrical disturbance and check that they have been eliminated after treatment, through localised heating of the tissue.
  • Promote the development of less invasive surgical techniques. For example, it should become possible to reliably replace heart valves percutaneously (passing through an artery), without having to open up the chest cavity, relying on location and algorithms and guiding the surgical instruments through the body.
  • Treating aneurisms (abnormal dilatation of the walls of a blood vessel) and stenoses (shrinking or narrowing of a major blood vessel). Current mini-invasive techniques are becoming increasingly complex, but thanks to TherA-Image, the surgeon can guide his/her instruments through the blood vessels using tools for planning the route (as for GPS) and effective assisted-imaging methods (enhanced reality) to reach the lesion and install a prosthesis at the site in complete safety.


Simplified dynamic 3D modelling of the Théra-Image room/©LTSI

TherA-Image is an instrument that has caused a major development in medical research and the occupational culture associated therewith, making it possible to design, deploy and assess the surgical interventions of tomorrow, to the benefit of the patient.

TherA-Image is financed through the State-Region Project Contract 2007-2013 in an amount of €5.2 million and has received support from the European Union (FEDER: €1.7 million), and the State (€2 million), the Brittany Region (€370,000), the General Council of Ille-et-Vilaine (€640,000) and from Rennes Métropole (€526,000).

Harmful effects of bisphenol A proved experimentally

Posted on by Priscille Rivière

Weak concentrations of bisphenol A are sufficient to produce a negative reaction on the human testicle. This has just been shown experimentally for the first time by René Habert and his colleagues (UMR Cellules souches et Radiations [UMR Stem Cells and Radiation], Inserm U 967 – CEA – Paris Diderot University) in an article that appeared in the journal entitled  Plos One.

Bisphenol A (BPA) is a chemical compound that is included in the composition of plastics and resins. It is used, for example, in the manufacture of food containers such as bottles and  babies’ feeding bottles. It is also found in the protective films used inside food and drink cans and on till receipts where it used as a discloser. Significant levels of BPA have also been found in human blood, urine, amniotic fluid and placentas. Recent studies have shown that this industrial component has harmful effects on reproductive ability, development and the metabolism of laboratory animals. BPA is strongly suspected of having the same effects on humans.

As a precautionary measure, the manufacture and sale of babies’ feeding bottles containing bisphenol A have been banned in Europe since January 2011. This ban will be extended in France to all food containers from July 2015. It will also be important to ensure that in the future, bisphenol A is not replaced by substitutes that have the same action.

Crédit photo : R habert/Inserm

System for culturing fœtal testicles developed by René Habert’s team. The testicles are sliced into tiny fragments then deposited on a filter in the centre of a petri dish. In an appropriate atmosphere, they are able to survive thus for several days, while secreting testosterone.

In an article published in Plos One, René Habert and his colleagues provide the first experimental proof that weak concentrations of bisphenol A are sufficient to produce a negative reaction on the human testicle.

No experimental study has shown hitherto that bisphenol A has a deleterious effect on male human reproduction and the few epidemiological studies that exist remain contradictory.

In collaboration with the Antoine-Béclère Hospital, Clamart1, researchers kept petri dishes of human fœtal testicles alive in the presence of bisphenol A or in the absence thereof, using an original procedure developed by this team. In 2009, this procedure made it possible to show for the first time, that phtalates (a different category of endocrine disruptors2  that are found in PVC, plastics, synthetic materials, sprays, etc.) inhibit the development of future spermatozoa in the human fœtus.

In this new study, researchers observed that exposure of human fœtal testicles to bisphenol A reduces the production of testosterone, and of another testicular hormone that is necessary for the testicles to descend into the sacs in the course of fœtal development. A concentration equal to 2 micrograms per litre of bisphenol A in the culture medium was sufficient to produce these effects. This concentration is equal to the average concentration generally found in the blood, urine and amniotic fluid of the population.

Testosterone is known to be produced by the testicle during the life of the fœtus, imposing masculinisation of the internal and external genitals which, in the absence of testosterone, develops spontaneously in the female direction. Furthermore, it is likely that testosterone also plays a role in the development of the testicle itself. Consequently, the current exposure of pregnant women to bisphenol A may be one of the causes of congenital masculinisation defects (of the hypospadia and cryptorchidism types) the frequency of which has doubled overall in the past 40 years. According to René Habert, “it is also possible that bisphenol A contributes to a reduction in the production of sperm and  the increase in the incidence of testicular cancer in adults that have been observed in recent decades”.

Furthermore, researchers have compared the response to bisphenol A in human fœtal testicles to those in the fœtal testicles of rats and  mice. “We have observed that the human species is far more sensitive to bisphenol A than the rat and the mouse. These results should encourage greater caution in regulatory toxicology in the extrapolation of data obtained on animals to define tolerable exposure thresholds in human health”, explains René Habert.

Finally, the researchers show in this article that Bisphenol A acts through a mechanism that is non-standard and that remains unknown but that it is important to identify in order to better understand the action of endocrine disruptors.

©Fotolia

Comment des souris subissant des agressions répétées développent une aversion sociale

Posted on by Priscille Rivière

Food insecurity attributed to future behavioural disorders in children

Posted on by Priscille Rivière

When a household experiences financial difficulties, the portion of the budget allocated to food is often restricted. In some cases, these difficulties may lead to food insecurity, i.e. limited and irregular access to a healthy and balanced diet. Based on a case study of 2,120 children, a team of Inserm researchers coordinated by Maria Mechior (Inserm Unit 1017 “Research Centre into epidemiology and population health”) has shown that children in food-insecure families have a high risk of developing long-term behavioural disorders, such as hyperactivity and attention deficiency.

This research has been published in the Plos One review. 

Food insecurity is defined as restricted, inadequate or uncertain access to healthy and nutritious food. It is mainly caused by financial difficulties and affects up to 10% of the general public. Previous research has shown that children who grow up in food-insecure families have a high level of psychological and behavioural problems; however, studies conducted to date did not distinguish the different types of behavioural difficulties and did not study relationships over the long-term.

This study conducted by Inserm researchers is based on data from a representative birth cohort of the Québec population. 2,120 children born in 1997-1998 were regularly monitored up to the age of eight. The researchers examined the link between food insecurity in children between 18 months and four and a half years and their behaviour between four and a half and eight years (i.e. the frequency of symptoms of depression/stress, aggression or hyperactivity/attention deficiency).

 5.9% of the children monitored experienced food insecurity during their early infancy. Compared to children who were not exposed to food insecurity, this group was three times more likely to develop long-lasting symptoms of hyperactivity and/or attention deficiency during childhood.

This link remains even when account is taken of family income and other characteristics that can be linked to food insecurity and the behaviour of children: single-parent families, parental psychopathology and negative behaviour of parents towards children. The link is therefore independent of these factors.

Food insecurity is a marker for particularly significant social and economic difficulties, of which the impact on the health of adults and children is known.

According to the researchers “Parents who are unable to regularly provide a satisfactory diet to the family may weaken the parent-child bond in early childhood, with effects on the long-term development of these children”.

Finally, food insecurity leads to changes in the diet of these families and generally results in the consumption of less fresh food and more foods that are high in fat and sugar. For some children, nutritional deficiencies (particularly iron), as well as excessive sugar intake, can result in hyperactive and inattentive behaviour.

For the researchers “reducing food insecurity in families could help reduce the frequency of behavioural disorders in young children”. 

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