Science + Technology

Breakdown of Myelin Insulation in Brain’s Wiring Implicated in Childhood Developmental Disorders, Addiction

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New evidence points to production of myelin, a fattyinsulation coating the brain's internal wiring, as a neural Achilles' heelearly in life.

An upcoming application of a novel model of human braindevelopment and degeneration pioneered by a UCLA neuroscientist identifiesdisruption of myelination as a key neurobiologicalcomponent behind childhood developmental disorders and addictive behaviors.

Detailed in an article in press with the upcoming annualpeer-reviewed publication Adolescent Psychiatry (Hillsdale, N.J.; The AnalyticPress Inc.; 2005) the analysis suggests that many factors can disrupt myelination and contribute to or worsen disorders such asautism, attention deficit/hyperactivity disorder and schizophrenia.

In addition, the analysis suggests that alcohol and otherdrugs of abuse have toxic effects on the myelinationprocess in some adolescents, contributing to poor treatment outcomes andexacerbating co-existing psychiatric disorders.

Author Dr. George Bartzokis, aprofessor of neurology at UCLA's David Geffen School of Medicine, concludesthat the high incidence of impulsive behaviors that characterize the teen yearsas well as many psychiatric disorders that occur in the teens and 20s arerelated to incomplete myelination of inhibitory "stop"brain circuits, while the "go" circuits become fully functional earlier indevelopment. These inhibitory circuits are not on line to quickly interrupthigh-risk behaviors that are so prevalent in teens and young adults.

"Myelination, a process uniquelyelaborated in humans, arguably is the most important and most vulnerableprocess of brain development as we mature and age," said Bartzokis,who directs the UCLA Memory Disorders and Alzheimer's Disease Clinic and theClinical Core of the UCLA Alzheimer's Disease Research Center.

"Environmental toxins,genetic predispositions and even diet appear to influence and sometimes disruptthis process," he added. "By shifting our research focus to medications thatact on brain metabolism and development, as opposed to brain neurotransmitterchemistry, neuroscientists will likely find a wealth of novel opportunities foraddressing the cause of brain disease rather than simply the symptoms."

Myelin is a sheet of lipid, or fat, with very highcholesterol content — the highest of any brain tissue. The high cholesterolcontent allows myelin to wrap tightly around axons, speeding messages throughthe brain by insulating these neural "wire" connections.

Bartzokis' analysis of magneticresonance images and post-mortem tissue data suggests that the production ofmyelin is a key component of brain development through childhood and well intomiddle age, when development peaks and deterioration begins (Neurobiology ofAging, January 2004). He also identifies the midlife breakdown of myelin as akey to onset of Alzheimer's disease later in life (Archives of Neurology, March2003; Neurobiology of Aging, August 2004).

"This model of a lifelong trajectory of brain developmentand degeneration embraces the human brain as a high-speed Internet rather thana computer," Bartzokis said. "The speed, quality, andbandwidth of the connections determine the brain's ability to processinformation, and all these depend in large part on the insulation that coatsthe brain's connecting wires."

Funders for the research includethe National Institute of Mental Health, the Research and Psychiatry Servicesof the Department of Veterans Affairs, the National Institute of AgingAlzheimer's Disease Center, and the Alzheimer's Disease Research Center ofCalifornia.

The UCLA Department of Neurology encompasses more than adozen research, clinical and teaching programs. These programs cover brainmapping and neuroimaging, movement disorders,Alzheimer's disease, multiple sclerosis, neurogenetics,nerve and muscle disorders, epilepsy, neuro-oncology,neurotology, neuropsychology,headaches and migraines, neurorehabilitation, andneurovascular disorders. The department ranks No. 2 among its peers nationwidein National Institutes of Health funding.

The Alzheimer Disease Research Center (ADRC) at UCLA,directed by Dr. Jeffrey L. Cummings, was established in 1991 by a grant fromthe National Institute on Aging. Together with grants from the Alzheimer'sDisease Research Center of California grant and the Sidell‑KaganFoundation, the center provides a mechanism for integrating, coordinating andsupporting new and on-going research by established investigators inAlzheimer's disease and aging. The Memory Disorders and Alzheimer's DiseaseClinic of the ADRC is an evaluation clinic for individuals over the age of 45who are experiencing mild but gradually progressing cognitive or memorydeclines that are not related to other brain diseases such as strokes, tumors,infection, metabolic abnormalities, psychiatric disease or trauma.

Additional online resources:

       David Geffen School of Medicine at UCLA:http://www.medsch.ucla.edu/

       UCLA Department of Neurology:http://neurology.medsch.ucla.edu/

       Alzheimer's Disease Research Center at UCLA:http://www.adc.ucla.edu/

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