Cholesterol, drugs responsible for depression: CCMB study

Hyderabad: The study of cholesterol and efficacy of drugs are especially relevant in the Indian context, as according to the National Mental Health Survey (2015-16), five percent of adults suffer from depression.

Prof. Amitabha Chattopadhyay’s group from the CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad study shows that the serotonin1A, receptor internalizes into cells through specialized regions of the cell membrane, called clathrin-coated pits, and thereafter recycles back to the cell membrane.

In a follow-up discovery, published in the American Chemical society journal, ACD Chemical Neuroscience, Prof. Chattopadhya’s group has now shown that modulating the levels of cholesterol, an important lipid in the cell-membrane, could change the mechanism of endocytosis of the serotonin1A receptor.

When the researchers from CCMB treated cells with statin, the fastest-selling cholesterol-lowering drug in the market, they observed that serotonin1A, receptor, instead of using clathrin-coated pits, internalized through alternate regions called caveolae, which are cave-like structures on the cell-membrane.

“We observed that this switch in the mechanism of internalization again reverted back to clathrin-coated pits when we put back cholesterol in cells that was lost upon statin treatment.” said Aditya Kumar, a Ph.D. student, who first authored the paper.

Interestingly, experiments from the team also revealed that receptors that usually recycle back to the cell membrane in normal conditions started getting degraded inside cells when they were treated with statin.

“We believe that our findings are crucial in understanding how cholesterol in cell membrane modulates the endocytosis of GPCR’s.” said Prof. Chattopadhyay.

An important class of anti-depressant drugs, termed selective serotonin reuptake inhibitors ( SSRI’s), target the endocytosis of the serotonin1A receptor as their mechanism of their action.

Prof. Chattopadhyay added that “from a biometrical standpoint, these results could provide novel insights into the mechanism underlying recent reports on the improved therapeutic activity of anti-depressant drugs when administered in combination with stains.”

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