The findings, published this week in The Journal of Neuroscience, may lead to more streamlined therapies for a variety of acute and chronic neurological disorders, including glaucoma and retinal artery occlusion.
In many neurodegenerative diseases, a main factor that kills neurons is excessive levels of glutamate, the most abundant excitatory neurotransmitter in many regions of the central nervous system (CNS). Diseases that occur as a result of high glutamate levels include hypoxic–ischemic brain injury (stroke), trauma, seizures, various forms of dementia and neurodegeneration. For years, the main explanation for the toxic effects of glutamate is that it overexcites neuronal cells via activation of glutamate receptors and thereby kills them.
"The most interesting aspect of our study and the reason we are so excited is that the pathway leading to glutamate-induced nerve cell death involves another vital player – namely, glial cells," says Dr. Adriana Di Polo, neuroscientist at the UdeM. "Through careful experimentation we now know that glutamate activates signaling pathways in glial cells that then lead to neuronal death."
Glial cells are the most abundant cell type in the nervous system and are traditionally thought of as 'partner' cells to nerve cells providing support, nutrients and an optimal environment. However, this study indicates that glial cells also have a more sinister side that allows them to induce or exacerbate neuronal death in pathological conditions.
"Neuronal cell death induced by glutamate is a key step in a large number of injury and disease settings and this study is important because it provides a road-map for the cellular and molecular events that allow this to occur" says Dr. Philip Barker, neuroscientist at the MNI, "The fact that specific signaling events in glial cells are important for inducing neuronal cell death is surprising and suggests new therapeutic targets for conditions that involve excitotoxicity."
The findings of the MNI and UdeM study represent a paradigm shift from the main model of excitotoxicity that has been in place for many years. Until now, the central idea has been that glutamate, which is released upon injury, binds to and activates the glutamate receptors on neurons triggering massive calcium entry and cell death. However, clinical trials targeting glutamate receptors have been disappointing suggesting that these receptors play only a minor role in triggering neuronal death.
The study, supported by the Canadian Institutes of Health Research, focused on nerve cells in the retina which convey information from the retina to the brain along the optic nerve, and are the primary link between the retina and the brain. The death of these retinal neurons from excess glutamate causes vision loss in various neurodegenerative disorders including optic neuropathies.
By disrupting signaling events in surrounding glial cells, the researchers were able to protect the majority of these neurons, confirming that glial cell events play a key role in death triggered by glutamate. This new understanding of the excitotoxic cascade of nerve cell death provides clear targets for successful therapeutic intervention of a wide-range of neurological and neurodegenerative diseases.
The MNI is a McGill University research and teaching institute, dedicated to the study of the nervous system and neurological diseases. Founded in 1934 by the renowned Dr. Wilder Penfield, the MNI is one of the world's largest institutes of its kind. MNI researchers are world leaders in cellular and molecular neuroscience, brain imaging, cognitive neuroscience and the study and treatment of epilepsy, multiple sclerosis and neuromuscular disorders. The MNI, with its clinical partner, the Montreal Neurological Hospital (MNH), part of the McGill University Health Centre, continues to integrate research, patient care and training, and is recognized as one of the premier neuroscience centres in the world. At the MNI, we believe in investing in the faculty, staff and students who conduct outstanding research, provide advanced, compassionate care of patients and who pave the way for the next generation of medical advances. Highly talented, motivated people are the engine that drives research - the key to progress in medical care. A new building, the North Wing Expansion, is currently under construction and will house state-of-the-art brain imaging facilities. Once the construction is completed and the new building is fully equipped, the scientific community focused on brain imaging research at the MNI will be without equivalent anywhere in the world.
Further reports about: > Health > Retina > cell death > central nervous system > chronic neurological disorders > degenerative diseases > glial cells > nerve cells > nervous system > neurodegenerative disease > neurological disease > optic neuropathies > pathological conditions > toxic effects of glutamate
A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital
Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences