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How metabolism and brain activity are linked

Study sheds light on why diet may help control seizures in epilepsy patients
Published: 16 January 2014

A new study by scientists at 平特五不中 and the University of Zurich shows a direct link between metabolism in brain cells and their ability to signal information. The research may explain why the seizures of many epilepsy patients can be controlled by a specially formulated diet.聽

The findings, published Jan. 16 in Nature Communications, reveal that metabolism controls the processes that inhibit brain activity, such as that involved in convulsions. The study uncovers a link between how brain cells make energy and how the same cells signal information 鈥 processes that neuroscientists have often assumed to be distinct and separate.聽

鈥淚nhibition in the brain is commonly targeted in clinical practice,鈥 notes Derek Bowie, Canada Research Chair in Receptor Pharmacology at 平特五不中 and corresponding author of the study. 鈥淔or example, drugs that alleviate anxiety, induce anesthesia, or even control epilepsy work by strengthening brain inhibition. These pharmacological approaches can have their drawbacks, since patients often complain of unpleasant side effects.鈥澛

The experiments showed an unexpected link between how the mitochondria of brain cells make energy and how the same cells signal information. Brain cells couple these two independent functions by using small chemical messengers, called reactive oxygen species (or ROS), that are normally associated with signaling cell death. While ROS are known to have roles in diseases of aging, such as Alzheimer鈥檚 and Parkinson鈥檚, the new study shows they also play important roles in the healthy brain. 聽

The findings emerged from an ongoing collaboration between Prof. Bowie鈥檚 laboratory in 平特五不中鈥檚 Department of Pharmacology and Therapeutics and a research team headed by Dr. Jean-Marc Fritschy, Professor of Pharmacology at the University of Zurich and current director of the Neuroscience Center Zurich (ZNZ).聽 The researchers have the longer term aim of trying to understand why the seizures of many epilepsy patients -- especially young children 鈥 can be treated with a high-fat, low-carbohydrate diet known as the ketogenic diet.聽

The idea that diet can control seizures was noticed as far back as ancient Greece, during periods of fasting. From the 1920s until the 1950s, the ketogenic diet was widely used to treat epilepsy patients. With the introduction of anticonvulsant drugs in the 1950s, the dietary approach fell out of favour with doctors. But because anticonvulsant drugs don鈥檛 work for 20% to 30% of patients, there has been a resurgence in use of the ketogenic diet.聽

鈥淪ince our study shows that brain cells have their own means to strengthen inhibition,鈥 explains Prof Bowie, 鈥渙ur work points to potentially new ways in which to control a number of important neurological conditions including epilepsy.鈥

The research was supported by funding from the Canadian Institutes of Health Research, the Swiss National Science Foundation, the聽--Neuroscience Science Center Zurich partnership, the Savoy Foundation and the Fonds de la recherche en sant茅 du Qu茅bec.聽

IMAGE: Neurons in the cerebellum.聽 CREDIT: Bowie Lab/平特五不中

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