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Press release
Brain researchers discover bright side of ill-famed molecule: nerve cells need cholesterol to establish contacts. New perspectives for the treatment of brain lesions | |||
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Paris, November 8, 2001 |
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A previously unknown role of cholesterol in the formation of contacts between nerve cells has been discovered by researchers (Science, 9th November 20011) at the Max-Delbrück-Center for Molecular Medicine in Berlin, Germany, and at the Centre de Neurochimie in Strasbourg, France (UPR 2356 CNRS). Their results suggest a link between brain cholesterol metabolism and nerve cell development, learning and memory and hint at new strategies to cure injury- or disease-induced brain lesions. The formation of synaptic connections between nerve cells is a decisive phase during brain development and plays an important role in learning and memory, but the mechanisms of this process are largely unknown. A previous study by Pfrieger and Barres 2 indicated that glial cells produce a synaptogenic factor. Glial cells form a large part of the brain tissue and support its development and function in many different ways. Pfrieger and Barres studied CNS neurons that can be purified by special isolation procedures and cultured under defined conditions in the absence of glia. They reported that neurons survive and grow under glia-free conditions, but show only few electrical signals that are generated by synapses. Soluble factors produced by specific types of glial cells, however, induced a strong potentiation of synaptic activity. Earlier this year, Pfrieger's group at the Max-Delbrück-Center for Molecular Medicine in Berlin and the Barres group at Stanford showed independently that the glial factor increases the number of synapses and their transmission efficacy3, but the identity of the glial factor remained unknown. In the last months, the group of Frank Pfrieger, who is now head of a bilateral research group of the Max-Planck Society and the Centre National de Recherche Scientifique at the Centre de Neurochimie in Strasbourg, achieved the final breakthrough. In the latest issue of Science, they report - quite surprisingly - that the long-sought factor is cholesterol! Cholesterol, which is an essential component of the plasma membrane, has a bad reputation, because high cholesterol levels in the blood raise the risk for atherosclerosis and consequently heart attack and stroke. The identification of cholesterol as synaptogenic factor shows a surprisingly beneficial side of this infamous molecule. The new results suggest that the availability of cholesterol in the brain limits the extent of synaptogenesis and that a defective cholesterol metabolism in the brain impairs its development and function. Neurons appear to produce enough cholesterol to survive and to grow, but require external cholesterol to form a sufficient number of synaptic contacts. Since cells in the brain cannot access the cholesterol supply in the blood, they need to synthesize cholesterol by themselves. According to the new results, glial cells produce surplus cholesterol and deliver it to neurons via lipoproteins. This dependence indicates a new role for glial cells as cholesterol providers and could explain why synaptogenesis in the CNS occurs after the differentiation of macroglial cells. The new results raise several questions: how does cholesterol promote synaptogenesis? Does it serve as building material for synaptic components or does it act as signal triggering subsequent cellular processes? Do changes in the cholesterol level in the brain influence mental development, learning or memory? Notably, the results imply a new hypothesis concerning Alzheimer's disease. Structural changes in apolipoprotein E, a crucial component of cholesterol carrier complexes, raise the risk for late-onset Alzheimer's disease. This may be due to an impaired supply of nerve cells with cholesterol and thus a reduced turnover of synapses. Together, the new results throw new light on an often disdained molecule and provide new perspectives for neurobiological research and strategies to cure brain lesions.
1 Mauch, D.H., Nägler, K., Schumacher, S., Göritz, C., Müller E.C., Otto, A., Pfrieger, F.W. CNS synaptogenesis promoted by glia-derived cholesterol. Science, 295 (2001). 2
Pfrieger, F.W., Barres, B.A. - Synaptic efficacy enhanced by glial cells.
Science, 277 : 1684-1687 (1997). 3
Nägler, K., Mauch, D., Pfrieger, F.W. - Glia-derived signals induce
synapse formation in neurones of the rat central nervous system. Journal
of Physiology, 533 : 665-679 (2001). Researcher
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