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Loss Of The Protein Target Of Lithium Disrupts Normal Mouse Embryonic Heart Development

Date:
October 3, 2008
Source:
Journal of Clinical Investigation
Summary:
One drug used to treat bipolar disorder is lithium, an inhibitor of GSK-3 proteins controversially linked to congenital heart defects. However, new data indicate that mice lacking GSK-3-beta die before birth, mostly at the late stage of embryonic development because of numerous defects in the heart. It is therefore suggested that it might be wise to exercise caution when considering whether to treat women of childbearing age with newer, more powerful GSK-3 inhibitors.
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One drug used to treat bipolar disorder is lithium, an inhibitor of GSK-3 proteins controversially linked to congenital heart defects. However, new data indicate that mice lacking GSK-3-beta die before birth, mostly at the late stage of embryonic development because of numerous defects in the heart. It is therefore suggested that it might be wise to exercise caution when considering whether to treat women of childbearing age with newer, more powerful GSK-3 inhibitors.

Individuals with bipolar disorder are usually treated with 'mood stabilizing' drugs, one of which is lithium — an inhibitor of GSK-3 proteins.

As new drugs that are more powerful inhibitors of GSK-3 are under development despite controversial studies suggesting a link between lithium therapy and congenital heart defects, Thomas Force and colleagues, at Thomas Jefferson University, Philadelphia, set out to determine whether GSK-3 proteins are important for heart development in mice.

In the study, mice lacking GSK-3-alpha were born with a normal heart; however, mice lacking GSK-3-beta died before birth. Some of the embryos died of severe liver degeneration approximately half way through gestation, but most died at the late stages of development.

These embryos exhibited numerous defects in the heart, including thickening of the heart muscle due to increased proliferation of the heart muscle cells. The authors therefore suggest that although controversy remains as to whether lithium is teratogenic, it would be wise to exercise caution when considering whether to treat women of childbearing age with the new generation of GSK-3 inhibitors.


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The above post is reprinted from materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal Reference:

  1. Deletion of GSK-3-beta in mice leads to hypertrophic cardiomyopathy secondary to cardiomyoblast hyperproliferation. Journal of Clinical Investigation, (in press)

Cite This Page:

Journal of Clinical Investigation. "Loss Of The Protein Target Of Lithium Disrupts Normal Mouse Embryonic Heart Development." ScienceDaily. ScienceDaily, 3 October 2008. <www.sciencedaily.com/releases/2008/10/081001181308.htm>.
Journal of Clinical Investigation. (2008, October 3). Loss Of The Protein Target Of Lithium Disrupts Normal Mouse Embryonic Heart Development. ScienceDaily. Retrieved July 5, 2015 from www.sciencedaily.com/releases/2008/10/081001181308.htm
Journal of Clinical Investigation. "Loss Of The Protein Target Of Lithium Disrupts Normal Mouse Embryonic Heart Development." ScienceDaily. www.sciencedaily.com/releases/2008/10/081001181308.htm (accessed July 5, 2015).

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