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Glia Gone Bad

Implicated in cancer, schizophrenia and chronic pain, these cells have become treatment targets.

By Lauren Ware // Spring 2011
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Nearly all forms of brain cancer arise from glial cells, not neurons (because mature neurons cannot undergo cell division, they almost never become cancerous). As researchers are finding, glia may be connected to many other types of brain disease and dysfunction. Here are some recent discoveries—and how they’re leading to treatments targeting glial cells.

BRAIN CANCER

TYPE OF GLIA IMPLICATED

Astrocytes, which are involved in a wide variety of brain functions, and oligodendrocytes, which sheathe the neurons’ axons in electricity-conducting myelin

SUSPECTED MECHANISMS

Chloride ions cause cells to swell with water. By expelling water, tightly packed cells can move through the brain. When a toxin that blocks chloride ion channels was given to rats with glia-derived brain cancer (gliomas), their tumors shrank.

POTENTIAL THERAPIES

A component of scorpion toxin, chlorotoxin, can cross the blood-brain barrier and block chloride ion channels in cells from glia-derived brain cancers only, sparing healthy cells. A synthetic version of the toxin, TM-601, is in clinical trials for gliomas in humans.

CHRONIC PAIN

TYPE OF GLIA IMPLICATED

Microglia, the immune cells of the brain, and astrocytes

SUSPECTED MECHANISMS

When microglia pick up chemical signals broadcast by injured nerve cells, they flood the area with cytokines, inflammatory molecules that cause pain sensations. For reasons unknown, this response sometimes continues long after the injury is healed.Microglia also have a receptor for cannabinoids, called the CB2 receptor, which relieves pain when activated. Astrocytes can become reactive after injury, causing inflammation and damage to surrounding cells, sometimes contributing to chronic pain.

POTENTIAL THERAPIES

Minocycline prevents microglia from being activated (and therefore releasing cytokines). Ibudilast and propentofylline inhibit reactive astrocytes. Sativex activates the CB2 cannabinoid receptors on microglia. It is in Phase III clinical trials. Fluorocitrate inhibits the cellular metabolism of astrocytes, thus depriving the cells of energy.

SCHIZOPHRENIA

TYPE OF GLIA IMPLICATED

Astrocytes

SUSPECTED MECHANISMS

Some schizophrenics have defects in the gene responsible for synthesizing the amino acid D-serine, which could contribute to symptoms. Astrocytes contain the enzyme that converts L-serine (also an amino acid) to D-serine.

POTENTIAL THERAPIES

Scientists are investigating ways to develop drugs that resemble D-serine to treat schizophrenia. (D-serine has been used in clinical trials and seems to be effective in treating the disease’s symptoms.)

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Glia’s Hidden Talents

glia

Each discovery adds to the sense that these long-ignored cells matter—for brain development, learning, memory and more.

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