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
Hot cars can hit deadly temperatures in as little as one hour
24.05.2018 | Arizona State University
3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
24.05.2018 | Ecology, The Environment and Conservation
24.05.2018 | Medical Engineering
24.05.2018 | Physics and Astronomy