New avenues of scientific exploration directed at glia.
Two research groups have turned the conventional wisdom about glial cellsâ€”that they do not form synapses with neuronsâ€”on its head, opening up new avenues of scientific exploration directed at glia. They have reported convincing evidence of synapses that directly link neurons with a type of glial cell in the corpus callosum, the white matter tracts that connect the brainâ€™s hemispheres. Their work is the latest chapter in a succession of unanticipated results that are challenging the long-held view of glia as the necessary but unremarkable supporting cast to the reigning star of the nervous system, the neuron. The new findings were reported in Nature Neuroscience in March by lead investigators Dwight Bergles of Johns Hopkins University, and Dirk Dietrich of the University Clinic Bonn in Germany. â€œThe two studies are beautifully done,â€ says Erik Ullian, who studies glial modulation of neuronal communication in development at University of California, San Francisco. â€œWhat is so surprising is that theyâ€™ve found these synaptic connections in the white-matter tracts.â€ Bergles agrees: â€œThe white matter has always been thought to be involved only in transmitting signals between different brain areas.â€ He likens the bundles of axons that make up white-matter tracts to â€œlittle highways through which you can conduct nerve signals, but thereâ€™s no off-ramp.â€ â€œWhat weâ€™ve shown is that those signals are actually communicating as they come down the axon. Theyâ€™re carrying information and there are cells that are receiving that information,â€ Bergles says. Stem Cell Reservoir? Bergles worked with mice that had been genetically modified with a fluorescent protein to light up a specific group of glial cells in the white matter. The targeted cells, so-called NG2+ cells, are a type of adult stem cell called precursor cells. They have attracted considerable interest from scientists because of their apparent ability to morph into various types of brain cells, including neurons. â€œThese cells seem to have an intrinsic multipotent capability,â€ says Bergles. â€œThatâ€™s why there is tremendous excitement about them, because they might be the largest pool of stem cells within the brain.â€ Under certain circumstances, NG2+ cells become oligodendrocytes, the glial cells that make the fatty sheath called myelin that envelops axons to speed the transmission of nerve signals. The Johns Hopkins researchers recorded the activity of NG2+ cells in brain samples taken from the fluorescent-tagged mice. What they found stunned them: clear synaptic connections between the NG2+ cells and axons running through the corpus callosum. â€œWe were shocked to see that they were detecting the same type of signaling that was occurring in the gray matter,â€ Bergles says: rapid release of glutamate that was being picked up by receptors on the surface of the NG2+ cells. Glutamate is one of the brainâ€™s most abundant neurotransmitters involved in neuron-to-neuron communications. â€œThis type of glutamate release was just not thought to occur within the white matter,â€ Bergles says. â€œThis study, along with our previous work, suggests that this signaling is ubiquitous among this population of NG2+ cells.â€ Questions and Clues â€œLike any good study, this one raises many more questions than it answers,â€ says Ullian. Itâ€™s possible, he says, that the synaptic connections â€œmay be required to keep NG2+ cells from proliferating out of control and producing too much myelin, or they may be providing some signal that keeps them in a predifferentiated state.â€ â€œThere are a lot of potential implications,â€ Bergles adds. â€œBut itâ€™s not clear at all why this mechanism exists and what itâ€™s being used for.â€ In laboratory studies, he notes, glutamate has been shown to alter the proliferation of NG2+ cells, clearly influencing the speed at which they divide and their potential to differentiate into other cell types. But, he cautions, â€œWe donâ€™t know yet if glutamate is working that way in the intact brain.â€ From a clinical standpoint, further research may provide clues to what goes wrong in demyelinating disorders such as multiple sclerosis, or in cerebral palsy, which is characterized by widespread damage to corpus callosum white matter. It could even help explain affective disorders such as depression and schizophrenia, which are thought to involve deficits in the connectivity and communication between specialized brain regions. â€œThere are several clues that tell us that after an injury, the brain tries to remyelinate,â€ says Vittorio Gallo, a glial cell researcher at Childrenâ€™s National Medical Center in Washington, D.C., who wrote a commentary in Nature Neuroscience accompanying the papers. â€œIt looks like the brain is trying to recapitulate something that happens early in development. If we can understand the developmental mechanism, we can devise strategies to repair the injured adult brain.â€
glial, glia, cells, neurons, white, matter, stem cell, corpus callosum, transmission, communication
- ID: 831
- Source: DNALC.G2C
It is increasingly clear that the nonneuronal brain cells called glia are intricately involved in the neuronal crosstalk at synapses.
Only quite recently have neuroscientists begun to understand the importance of white matter, a long-neglected part of the brain.
Professor Wayne Drevets explains that specific glial cells known as oligodendrocytes may be decreased in the brains of individuals who have bipolar disorder or major depressive disorder.
Many psychiatrists are now prescribing second-generation or 'atypical' antipsychotics.
Research continues to show that stem cells could be harnessed for therapeutic purposes.
The corpus callosum consists of a large bundle of fibers connecting the right and left hemispheres of the brain. Each hemisphere controls movement in the opposite side of the body.
An overview of bipolar disorder-related content on Genes to Cognition Online.
Professor David Anderson describes the types and properties of different stem cells. The most well known, embryonic stem cells, are the most flexible.
Doctor Brian Bacskai define astrocytes, or astroglia as brain cells that have an active structural role in keeping the brain together.
Professor Pat Levitt describes how progenitor cells can be manipulated to develop into a particular type of neuron.