Reduce fat, increase anxiety
doi:10.1038/nindia.2010.83 Published online 21 June 2010
New research has shown that mevastatin, a cholesterol-lowering drug, may affect the activity of the serotonin1A receptor. This receptor is bound to nerve cell membranes, and its inactivity has previously been linked to anxiety and mood disorders.
Cholesterol is an important lipid because it is known to regulate the function of membrane receptors — neuronal receptors in particular. To explore how cholesterol-lowering drugs affect the activity of the serotonin1A receptor, the researchers carried out experiments with three types of cells — fluorescent protein-tagged Chinese hamster ovary (CHO) cells (control), cholesterol-treated CHO cells and cholesterol-replenished CHO cells. They used mevastatin as a cholesterol-lowering drug that inhibits the activity of HMG-CoA reductase, leading to cholesterol depletion.
CHO cells expressing human serotonin receptors were treated with mevastatin. This treatment caused a decrease in cholesterol content and therefore a significant reduction in the activity of serotonin receptors. When the CHO cells were replenished with cholesterol, the activity of the serotonin receptors was restored. The study suggests that the interaction between cholesterol and receptors such as serotonin1A is crucial for normal brain operation.
"There is growing concern in the medical community that the chronic use of cholesterol-lowering drugs causes depression and anxiety," says lead researcher Amitabha Chattopadhyay. "Our work is the first step towards finding the molecular evidence that could pin down such a relationship."
- Shrivastava, S. et al. Chronic cholesterol depletion using statin impairs the function and dynamics of human serotonin1A receptors. Biochemistry. doi: 10.1021/bi100276b (2010)