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Jul 3, 2008

Statins Found to Affect Glial Progenitor Cells

  • Statins affect glial progenitor cells, which are important to brain health as we age, according to a group of scientists. These cells are similar to stem cells and can become either astrocytes or oligodendrocytes. The researchers found, however, that statins caused the glial progenitor cells to turn into only oligodendrocytes.

    “This might reduce the available progenitor pool and hence degrade the long-term regenerative competence of the adult white matter,” the authors suggest in their paper, which appears in the July issue of Glia.

    The team conducted experiments in cell culture using human brain cells and exposing them to doses of statins. They ran a screen to see which genes are more active in these cells compared to other brain cells. They found several related to cholesterol, including the enzyme HMG-CoA reductase, which is the main target of statins.

    “It was quite surprising that the cholesterol-signaling pathways are so active in these cells,” notes Steven Goldman, M.D., Ph.D., a neurologist at University of Rochester Medical Center, who led the team. “Since such signaling is blocked with compounds used literally by millions of patients every day, we decided to take a closer look.”

    The team measured the effects of two widely used statins, simvastatin and pravastatin, on glial progenitor cells. They looked at progenitor cells from 16 patients who had brain tissue removed during surgery to treat epilepsy, tumors, or vascular problems.

    The scientists found that both compounds, when used at normal doses, trigger glial progenitor cells to develop into oligodendrocytes. For example, in one experiment, they found about five times as many oligodendrocytes in cultures of human progenitor cells exposed to pravastatin compared to cultures not exposed to the substance. Also, they found that the number of progenitor cells was just about one-sixth the level in cultures exposed to simvastatin compared to cultures not exposed to the compound.

    The body maintains a pool of uncommitted glial progenitor cells as a reservoir that is tapped into when it needs to repair damage, the researchers explain. No one knows the consequences if such cells weren't available when needed, though increased cognitive impairment might be one possibility, they add.

    This study may be relevant to diabetic drugs as well, the investigators report. They discovered that when a signaling molecule called PPAR gamma was blocked, statins no longer affected glial progenitor cells. Since PPAR gamma is the main target of diabetes medications such as Avandia and Actos, which trigger the molecule, Dr. Goldman notes that it is likely that those drugs have the same effect on progenitor cells. He also noted that many patients are on both diabetes drugs and statins, which could increase the effect.

    “There has been a great deal of discussion about a link between statins and dementia, but evidence either way has been scant,” says Dr. Goldman. “This new data provides a basis for further exploration. There are a great number of questions that need to be explored further before anyone considers changing the way statins are used.”

    The research group also included a Cornell scientist.


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