Everyone knows that neurons talk to each other - that's their main job. But neurons also talk to the cells around them. The communication between neurons and support cells is important for the healthy functioning of the brain. But does it play a role in disease too?
Jeffrey Rothstein, a professor of neurology and neuroscience, shows that the failure of this communication can indeed contribute to neurological illness.
Specifically, his group demonstrated that neurons in amyotropic lateral sclerosis (ALS), also known as Lou Gehrig's disease, suffer from a failure to communicate with helper cells called astrocytes. The results appear in last week's issue of Neuron.
Astrocytes are support cells in the central nervous system that nourish and keep neurons alive. These sidekick cells also play crucial roles in regulating neuronal communication.
Some neurons release a chemical called glutamate in order to pass on their message to the next neuron. Unfortunately, if a neuron gets too excited, it releases too much glutamate, which is toxic to cells in high doses.
Usually, the ever-helpful astrocytes would take care of the mess, sucking up any superfluous glutamate and processing it in order to keep the neurons running happily and healthily. But when this "mopping-up" mechanism fails, glutamate builds up until it starts a cascade of cell death.
This process, which can turn suddenly into a death spiral for the entire affected organism, seems to be key in the advancement of several neurological disorders, including in ALS. Scientists call this process "glutamate excitotoxicity."
The cascade can be initiated in any number of ways, including cell damage, neuron degeneration or toxicity. But from there the pattern is the same, and the results are equally terrible: Dying neurons can no longer signal to astrocytes to keep them alive, healthy and doing their jobs.
Rothstein's group has shown that sick neurons tell astrocytes to kill themselves. These dying astrocytes are less able to mop up excess glutamate, which causes further neuron death. These causes and effects form a cycle that, if unchecked, lead to the unabated death of many cells.
Normal function begins to be impaired as fewer neurons are available to complete the needed neural circuits, and eventually the majority of function can be lost due to this destructive mechanism.
This finding has given scientists a strong reason to more closely study the synaptic relationships between astrocytes and neurons in neurological diseases. Rothstein's findings suggest that disrupted communication between neurons and astrocytes may be the factor that allows diseases to spread quickly and seemingly unstoppably.
Further study may lead to the discovery of how to slow or even stop this degenerative and destructive process, in the hopes of preserving astrocyte-neuron connections and brain function.
