Researchers uncover a crucial link between protein synthesis and autism spectrum disorders
Researchers from McGill University and the University of Montreal have identified a crucial link between protein synthesis and autism spectrum disorders (ASD), which can bolster new therapeutic avenues. Regulation of protein synthesis, also termed mRNA translation, is the process by which cells manufacture proteins. This mechanism is involved in all aspects of cell and organism function. A new study in mice has found that abnormally high synthesis of a group of neuronal proteins called neuroligins results in symptoms similar to those diagnosed in ASD. The study also reveals that autism-like behaviors can be rectified in adult mice with compounds inhibiting protein synthesis, or with gene-therapy targeting neuroligins. Their results are published in the journal Nature.
Autism spectrum disorders (ASD) encompass a wide array of neurodevelopmental diseases that affect three areas of behaviour: social interactions, communication and repetitive interests or behaviors. According to the U.S.-based Centers for Disease Control and Prevention, 1 in 88 children suffer from ASD, and the disorder is reported to occur in all racial, ethnic, and socioeconomic groups. ASDs are almost five times more common among boys (1 in 54) than among girls (1 in 252).
"My lab is dedicated to elucidating the role of dysregulated protein synthesis in cancer etiology. However, our team was surprised to discover that similar mechanisms may be implicated in the development of ASD", explained Prof. Nahum Sonenberg, from McGill's Dept. of Biochemistry, Faculty of Medicine, and the Goodman Cancer Research Centre. "We used a mouse model in which a key gene controlling initiation of protein synthesis was deleted. In these mice, production of neuroligins was increased. Neuroligins are important for the formation and regulation of connections known as synapses between neuronal cells in the brain and essential for the maintenance of the balance in the transmission of information from neuron to neuron."
"Since the discovery of neuroligin mutations in individuals with ASD in 2003, the precise molecular mechanisms implicated remain unknown," said Christos Gkogkas, a postdoctoral fellow at McGill and lead author. "Our work is the first to link translational control of neuroligins with altered synaptic function and autism-like behaviors in mice. The key is that we achieved reversal of ASD-like symptoms in adult mice. Firstly, we used compounds, which were previously developed for cancer treatment, to reduce protein synthesis. Secondly, we used non-replicating viruses as vehicles to put a break on exaggerated synthesis of neuroligins."
Computer modeling played an important role in this research. "By using a new sophisticated computer algorithm that we specially developed to answer Dr. Sonenberg's questions, we identified the unique structures of mRNAs of the neuroligins that could be responsible for their specific regulation," explained Prof. François Major, of the University of Montreal's Institute for Research in Immunology and Cancer and Department of Computer Science.
The researchers found that dysregulated synthesis of neuroligins augments synaptic activity, resulting in an imbalance between excitation and inhibition in single brain cells, opening up exciting new avenues for research that may unlock the secrets of autism.
"The autistic behaviours in mice were prevented by selectively reducing the synthesis of one type of neuroligin and reversing the changes in synaptic excitation in cells," explained Prof. Jean-Claude Lacaille at the University of Montreal's Groupe de Recherche sur le Système Nerveux Central and Department of Physiology. "In short, we manipulated mechanisms in brain cells and observed how they influence the behaviour of the animal." The researchers were also able to reverse changes in inhibition and augment autistic behaviors by manipulating a second neuroligin. "The fact that the balance can be affected suggests that there could be a potential for pharmacological intervention by targeting these mechanisms," Lacaille concluded.
Journal reference: Nature
Provided by University of Montreal
- Autism-related Proteins Control Nerve Excitability, Researchers Find Jun 20, 2007 | not rated yet | 0
- When nerve cells can’t make contact Sep 22, 2006 | not rated yet | 0
- Further support for a role of synaptic proteins in autism spectrum disorders Feb 09, 2012 | not rated yet | 0
- Misfolded neural proteins linked to autism disorders Sep 10, 2010 | not rated yet | 0
- New light on genetics of autism Sep 14, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Image of a Convex Lens Cut in Half Horizontally
39 minutes ago Hello everyone, A friend of mine came up with this question in class and I really do not have a good answer. Suppose you have a convex lens...
Ray tracing throught optical system of thick lenses
48 minutes ago Can you advise me a free software that allow to draw rays passed throught system of thick lenses (preferable in 3D)?
Faraday's law on circular wire
1 hour ago In my examples on Faraday's law in my book, they use a drawing of a magnet approaching a circular wire. The changing magnetic flux then induces an...
Specific Exergy vs Specific Flow Exergy
3 hours ago I'm having some difficulty understanding exactly what the difference between the definitions of these values are. As I understand it, in terms of...
The Durability of Bone: Long Falls
11 hours ago I am doing a paper on the physics in Valve's Portal and got interested in the "Long Fall Boots" that prevent any damage no matter how far you fall. I...
Is energy convertible to matter?
13 hours ago Can we convert energy to matter?
- More from Physics Forums - Classical Physics
More news stories
Children with autism showed significant improvement after six months of simple sensory exercises at home using everyday items such as scents, spoons and sponges, according to UC Irvine neurobiologists.
Autism spectrum disorders 20 hours ago | 3 / 5 (1) | 0 |
Research by Victoria University PhD education graduand Larah van der Meer highlights the importance of understanding the communication preferences of children with developmental disabilities such as autism.
Autism spectrum disorders May 14, 2013 | 3.3 / 5 (3) | 1
At times, Andy Shih still finds himself overwhelmed by the groundswell of interest in autism applications he's seen in the three years since Apple Inc. released the first iPad.
Autism spectrum disorders May 09, 2013 | 2 / 5 (1) | 0
Children with autism see simple movement twice as quickly as other children their age, and this hypersensitivity to motion may provide clues to a fundamental cause of the developmental disorder, according ...
Autism spectrum disorders May 08, 2013 | not rated yet | 0 |
(AP)—Autism scientists are seeking more brain samples for research.
Autism spectrum disorders May 02, 2013 | 5 / 5 (1) | 0
Research presented today shows that high-fructose corn syrup can cause behavioural reactions in rats similar to those produced by drugs of abuse such as cocaine. These results, presented by addiction expert Francesco Leri, ...
7 minutes ago | not rated yet | 0
(Medical Xpress)—High blood pressure is something that has traditionally been a problem in Scotland, but might there be a link to our climate?
1 hour ago | not rated yet | 0
(Medical Xpress)—Health care spending is much higher for older Americans than for younger adults and children, on average, and analysts have said that increasing spending leads to longer life expectancy.
56 minutes ago | not rated yet | 0
The DESolve bioresorbable coronary scaffold system achieves good efficacy and safety with low rates of late lumen loss and major coronary adverse events at six months, show first results from the pivotal DESolve Nx trial ...
38 minutes ago | not rated yet | 0
More than 40 percent of patients being treated for COPD at a federally funded clinic did not have the disease, researchers found after evaluating the patients with spirometry, the diagnostic "gold standard" for chronic obstructive ...
36 minutes ago | not rated yet | 0
Results from a large observational study reported at EuroPCR 2013 today question whether bivalirudin is superior to heparin in the absence of GPIIb/IIIa blockade, showing similar 30-day mortality in patients with non-ST segment ...
36 minutes ago | not rated yet | 0