Unlock Autism

The development, maintenance, and repair of myelin is the single most important factor affecting cognition and behavior, according to a UCLA neurology professor who has collected extensive data on the nerve insulator. In an article to be published in an upcoming issue of Biological Psychiatry, George Bartzokis, MD, asserts that myelin may be the universal cause or contributor to a wide range of neuropsychological brain disorders, from autism to Alzheimer’s disease. Dr. Bartzokis, who directs the UCLA Memory Disorders and Alzheimer’s Disease Clinic in Los Angeles, suggests that using noninvasive imaging technology to view the miles of myelin in the brain as it grows and breaks down throughout a human life cycle may offer insights leading to the development of new treatments for brain disorders. Nicotine, which studies have suggested enhances the growth and maintenance of myelin, could be one such novel treatment.

In some of the first research to approach brain disorders from a myelin-centered point of view, Dr. Bartzokis studied the effects of cholinergic treatments, including acetylcholinesterase inhibitors (AChEIs) that are used to improve a neuron’s synaptic signaling in people with diseases such as Alzheimer’s. Some data suggest that such treatments may even modify or slow the progression of Alzheimer’s as well as other diseases.

Nicotine, Age, and Disease

Dr. Bartzokis hypothesizes that cholinergic stimulation at neuronal synapses affects the myelination process throughout brain development in the course of a human’s lifetime.He found in clinical trials that cholinergic treatment protects brain cells, while postmortem and imaging data have shown cholinergic receptor changes during brain development and degeneration. Trials have also revealed epidemiologic evidence that nicotine from tobacco may have a protective effect on degenerative diseases of old age and younger psychiatric populations. Cholinergic treatments have also shown efficacy in the aging process and age-related neurodegenerative diseases such as Alzheimer’s disease, as well as some neurodegenerative diseases like autism and ADHD.

According to Dr. Bartzokis, myelination development resembles an inverted “U” over the course of a lifetime, with increasing myelin development peaking in middle age and breaking down and declining in later years. Following the analogy of the Internet, Dr. Bartzokis says the “connectivity” provided by myelination increases speed by 10-fold and decreases refractory time by 34-fold. Thus, myelination increases the “bandwidth,” or processing capacity, of our brain’s Internet by 340-fold and is “indispensable for developing our uniquely elaborate higher cognitive functions.”

Different cortical regions myelinate at different ages, with later-myelinating oligodendrocytes growing increasingly more complex as we age. Irregular development during the most complex stages of the myelination process contributes to several of the neuropsychiatric disorders that tend to manifest in the early years. These disorders—eg, autism, ADHD, schizophrenia, mood disorders, addictions—are defined by overlapping cognitive and behavioral symptom clusters.

According to Dr. Bartzokis, healthy individuals with normal myelin development typically lose 45% of their myelinated fiber length when they reach the degeneration phase in adulthood. This change in the brain may cause progressive losses of memory and cognitive functions, as well as mild to severe behavioral changes.

The loss of myelin and its components such as sulfatide, myelin basic protein, and cholesterol begins early in the development of Alzheimer’s disease, well before diagnosis of dementia or mild cognitive impairment. The myelin breakdown process is further modified by risk factors such as the presence of APOE ε4 or environmental factors such as a head trauma.

Nicotine’s Effect on Myelination and Repair

Recent research has unveiled some surprising findings on the influence of nicotine on myelination and the aging process. Direct nicotinic stimulation associated with smoking has been shown to increase nicotinic receptors in the late myelinating frontal and temporal intracortical regions. Unlike most agonists, nicotine causes an up-regulation of its receptors and has been shown to accelerate brain function recovery when white matter is damaged.

Nicotine dependence is common among people with psychiatric disorders. Some researchers have suggested the high prevalence of nicotine use among the psychiatric population represents an unconscious effort to “self-medicate.” Research on proteins has suggested that nicotine may marginally increase the expression of myelin proteins; other addictive drugs (eg, cocaine, alcohol) along with developmental diseases (eg, schizophrenia, bipolar disorder, depression) show a decrease of these proteins.

Other research has found an association between nicotinic stimulation and protective effects in schizophrenia and autism, where cortical myelination deficits have been documented. While nicotine has well-known negative effects on overall health, smoking during later years is also associated with a reduced likelihood of the development of degenerative conditions like Alzheimer’s and Parkinson’s diseases. Using the myelin-centered model, the apparent beneficial aspects of smoking on brain disorders can be attributed to nicotine’s stimulation of oligodendrocyte precursors. Dr. Bartzokis believes that nicotine, delivered through a patch, not through smoking cigarettes, should be studied for its efficacy in promoting the growth and maintenance of myelin, and that AChEIs “deserve much closer scrutiny” as a therapy for the prevention of both developmental and degenerative brain disorders.

—Kathlyn Stone http://www.neuropsychiatryreviews.com/07jan/myelin.html

Share It

Hide Sites

Research: “The Myelin Project”:

The exciting work of researchers funded by The Myelin Project, whose goal is to remyelinate the human central nervous system, may someday have benefits for autistic children. Only time will tell if a specific area of damaged neurons can be found and potentially repaired with stem cells.

The first human trial, conducted by Dr. Timothy Vollmer at Yale University School of Medicine, will attempt to transplant myelin-forming Schwann cells into the brains of five patients with multiple sclerosis. The cells will be obtained from the sural nerves of the patients themselves. Although Schwann cells normally produce myelin in the peripheral nervous system, several recent experiments conducted on rodents and cats have shown these cells have the ability to remyelinate in the CNS as well.

While multiple sclerosis is a long way from autism, there is discussion of anti-myelin antibodies in autism, and there is talk of inflammatory processes involving myelin. Whether this technology can help autism if it works for multiple sclerosis is anybody’s guess, but it’s exciting to wonder about.

The Myelin Project funds a Cell Culture Unit at the University of Wisconsin-Madison, where Dr. Su-chun Zhang continues to generate cultures with ever-higher percentages of human oligodendrocyte precursors (OPs). Oligodendrocytes are the cells that normally myelinate the CNS. If obtainable in sufficient quantity, they would provide an alternative to Schwann cells for transplantation. The Unit has developed a method to track transplanted OPs by MRI, labeling the cells with iron particles. In another recent experiment, Dr. Baron-Van Evercooren and colleagues were able to remyelinate as many as 55% of the nerves in monkey spinal cord lesions by transplanting the monkeys’ own Schwann cells. These initial positive results, however, have not been confirmed in subsequent attempts. She suspects that the viral labels she used to distinguish the transplanted cells caused them to die. She is trying again without viral labeling. If successful, this experiment would prove that CNS remyelination is feasible in higher animals.

Several researchers funded by The Myelin Project have injected myelin-forming cells into the ventricles of the brain of experimental animals and have shown that these cells were transported by the cerebrospinal fluid to all regions of the brain. This makes it more likely that injected cells will travel to where the myelin needs to be repopulated.

The Myelin Project has funded Dr. Oliver Br�stle of the University of Bonn, Germany, and Dr. Evan Snyder of Harvard University to work with neural stem cells (NSC). These are self-renewing, multipotent cells, capable of differentiating into the major types of neural cells, including oligodendrocytes. One of their most potentially beneficial properties is their tendency to respond to signals in the CNS environment. In CNS diseases, these signals guide the cells to damaged areas. Second, they prompt them to differentiate into the specific cell type needed for the repair — neurons in nerve diseases like Parkinson’s and oligodendrocytes in myelin disorders like the leukodystrophies and multiple sclerosis.

NSCs are typically of fetal origin, but have also been found in the adult brain. NSCs can be multiplied in culture indefinitely as an “immortal” cell line. They could eventually provide an inexhaustible source of myelin-forming cells, eliminating the need for obtaining them from fresh tissue. Several research centers are now testing human NSCs to verify their safety and in particular to rule out any risk of their becoming cancerous. If this testing concludes favorably, then prospective myelin repair strategies could take a two-fold approach. NSCs would be injected into the ventricular system where the cerebrospinal fluid would circulate them to all parts of the CNS. Local signals would then come into play, guiding the cells to the specific demyelinated areas.

The Myelin Project has also funded Dr. Robin Franklin of the University of Cambridge to study olfactory ensheathing cells, a third type of myelin-producing cell. He has perfected a technique for demyelinating the area of rat brain connecting the cerebellum with the brain stem. He subsequently remyelinated the area by transplanting rat Schwann cells, which adds to the body of evidence in favor of Schwann cell transplantation as a way of repairing CNS myelin lesions.

The Myelin Project has also funded Dr. Inderjit Singh of the Medical University of South Carolina to study the use of Lovastatin in the treatment of myelin disorders. The drug corrects the biochemical defect of adrenoleukodystrophy, lowering the levels of very long chain fatty acids in plasma. Preliminary studies with an animal model of MS have confirmed Lovastatin’s ability to block the induction of cytokines, substances responsible for the inflammation of the CNS. We know that the levels of very long chain fatty acids and of some cytokines are elevated in autism. I am wonderijng already if Lovastatin might be worth trying for children with documented elevated very long chain fatty acids and elevated cytokines.

These studies present exciting possibilities for the future for treating neurodegenerative diseases. They may eventually have relevence for such diverse conditions as autism, cerebral palsy, and CNS vaccine damage syndromes. Time will tell.

find more at http://www.healing-arts.org/children/cell.htm

Share It

Hide Sites