Blame myelin for many neuropsychiatric disorders

New understanding could lead to novel treatments -- including a use for nicotine

What makes the human brain unique? Of the many explanations that can be offered, one that doesn't come readily to mind is -- myelin.

Conventional wisdom holds that myelin, the sheet of fat that coats a neuron's axon -- a long fiber that conducts the neuron's electrical impulses -- is akin to the wrapping around an electrical wire, protecting and fostering efficient signaling. But the research of UCLA neurology professor George Bartzokis, M.D., has already shown that myelin problems are implicated in diseases that afflict both young and old -- from schizophrenia to Alzheimer's.

Now, in a report published in the journal Biological Psychiatry and available online, Bartzokis argues that the miles of myelin coating in our brain are the key "evolutionary change that defines our uniqueness as a species" and, further, may also be the cause of "our unique vulnerability to highly prevalent neuropsychiatric disorders." The paper argues that viewing the brain as a myelin-dependent "Internet" may be key to developing new and novel treatments against disease and aid in assessing the efficacy of currently available treatments, including the use of nicotine (delivered by a patch, not smoking), which may enhance the growth and maintenance of myelin.

Myelin, argues Bartzokis, who directs the UCLA Memory Disorders and Alzheimer's Disease Clinic, is "a recent invention of evolution. Vertebrates have it; invertebrates don't. And humans have more than any other species."

Bartzokis studied the reported effects of cholinergic treatments, using drugs that are known to improve a neuron's synaptic signaling in people who suffer diseases like Alzheimer's. Furthermore, he notes, some clinical and epidemiological data suggest that such treatments may modify or even delay these diseases

Looking at such effects from a myelin-centric point of view, Bartzokis argues that cholinergic treatments may have nonsynaptic effects as well, perhaps by enhancing myelination and myelin repair -- and the better the myelin, the more efficient the neuron signaling and our "Internet's" function. Specifically, such cholinergic treatments may enhance oligodendrocytes, a type of glia cell in the brain that produces myelin during the brain 's development and constantly maintains and repairs it as we age.

While more work needs to be done to fully understand the role of nonsynaptic cholinergic effects on brain development, said Bartzokis, his hypotheses can easily be tested through in vivo imaging of the brain to study the breakdown and growth of myelin. That will make it possible to directly test in humans the practical utility of the myelin-centered model of the human brain.

Ultimately, it could foster the development of novel treatments, as well as aid in assessing the efficacy of currently available treatments. These include the use of cholinergic treatments that include acetylcholinesterase inhibitors (used to treat Alzheimer's) and nicotine patches.

"Through these rather benign interventions," Bartzokis said, "such effects on the brain's vulnerable oligodendrocyte populations may offer exciting opportunities for the prevention of both developmental and degenerative brain disorders. They deserve much closer scrutiny."

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Bartzokis work was supported in part by a National Institute of Mental Health grant, a National Institute on Aging Alzheimer's Disease Center Grant, Research and Psychiatry Services of the Department of Veterans Affairs and the Sidell-Kagan Foundation.

The UCLA Department of Neurology encompasses more than a dozen research, clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranked No. 1 in 2005 among its peers nationwide in National Institutes of Health funding. For more information, see http://neurology.medsch.ucla.edu/.


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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