When intracellular cholesterol is lowered profound degradation of controlling vital cell interactions

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Cholesterol Levels Critical for Golgi Apparatus Function Another Mechanism for Statin Associated Behavioral Change http://www.spacedoc.net/statins_behavior.html We now have thousands of case reports of statin associated behavioral change. Road rage, extraordinary hostility, profound depression, even basic personality changes (“that is not my husband”) are frequently reported. In my book, Statin Drugs Side Effects, I have mentioned the Golgi apparatus in my discussions of neuropeptide formation and function, key to explaining behavioral side effects of the statin class of drugs. I have previously postulated a possible role of statins on this extremely complex structure. The Golgi apparatus, along with a tubular network called the endoplasmic reticulum, is present in every cell in our body, controlling vital cell interactions. Now our scientists are just beginning to reveal the actual mechanics of cholesterol’s role in statin associated behavioral change – another pathway not yet dreamed of only a year ago. Reporting in Science recently, Wang and Anderson have discovered a critical role for cell cholesterol in the Golgi apparatus role of cell signaling. They found that oxysterol binding protein (OSBP) is a cholesterol-binding “scaffolding” protein vital to the control of signaling pathways within the Golgi apparatus. These researchers found this vital pathway extremely sensitive to cholesterol levels within the cells. When intracellular cholesterol was lowered by whatever means, profound degradation of this signaling pathway resulted. Although statins were not used in this experiment, there is no doubt that the effects of statins on this pathway could be profound in susceptible individuals. This adds another mechanism, that of intracellular cholesterol lowering, to the already established mechanism of dolichol inhibition in explaining the great variety of behavioral side effects associated with statin drug use. Both of these mechanisms come to play in the delicate process of neuropeptide formation and transport through the Golgi apparatus and endothelial reticulum. These peptides then must pass through the central canals of our axons to receptors elsewhere in the body. Just the process of axonal delivery of biochemicals is completely alien to most physicians trained earlier than 1980. Physicians then had no information either of neuropeptides or this novel delivery system in their training, so digesting the potential effects of a statin drug on signaling systems within the Golgi apparatus and altered neuropeptide formation during transit through the endoplasmic reticulums does not come easily to their understanding. Even younger doctors are surprised to learn that cellular inter-communication, our very thoughts, sensation and emotions, are no longer the province of our traditional hormonal and autonomic nervous system but rather this novel neuropeptide thing. Is it any surprise they many physicians have difficulty accepting that such behavioral changes as aggressiveness, hostility, homicidal thoughts, depression and suicide are associated with statin drug use? Duane Graveline MD MPH