Statins May Cause Long-Term Brain Injury

Statins, drugs widely used to control cholesterol levels, may have a long-term detrimental effect on the brain by stimulating glial progenitor stem cells to differentiate preferentially into oligodendrocytes.

Glial progenitor cells, which comprise about 3% of brain cells, are distributed throughout the brain. They represent a reservoir of uncommitted stem cells that can be called upon to replenish brain tissue injured by trauma or disease.

In the current study, investigators from the University of Rochester (NY, USA) looked at the effect of statins, drugs that shut down cholesterol synthesis, on the fate of glial progenitor cells.

They reported in the July 2008 issue of the journal Glia that glial progenitor cells abundantly express the enzyme HMG-CoA reductase, which is the primary target of statin activity. They then used two statins, simvastatin, or pravastatin, to treat cultures of glial progenitor cells that had been obtained from 16 patients who had brain tissue removed during surgery to treat epilepsy, tumors, or vascular problems.

Results revealed that both statins induced a dose-dependent transformation of progenitor cells into mature cells of the oligodendrocyte phenotype with concomitant reduction in the number of undifferentiated progenitor cells. This reduction in the size of the available progenitor pool might degrade the long-term regenerative competence of the adult white matter and interfere with the brain's ability to repair itself.

"There has been a great deal of discussion about a link between statins and dementia, but evidence either way has been scant,” said senior author Dr.. Steven Goldman, professor of neurology at the University of Rochester. "It was quite surprising that the cholesterol-signaling pathways are so active in these cells. These findings were made through experiments done in cell culture using human brain cells and exposing them to doses of statins used widely in patients. But this research was not done in people. There are a great number of questions that need to be explored further before anyone considers changing the way statins are used.”


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