Cell's split personality is a major discovery into neurological diseases

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Cell's split personality is a major discovery into neurological diseases

http://www.eurekalert.org/pub_releases/2009-05/mu-csp050709.php

Researchers at the Université de Montreal (UdeM) and the Montreal Neurological

Institute (MNI), McGill University have discovered that cells which normally

support nerve cell (neuron) survival also play an active and major role in the

death of neurons in the eye. 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. 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.