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Female Brain Cells Better Able to Survive Starvation than Male Ones, Pitt Researchers Say ​

PITTSBURGH, January 23, 2009 — Neurons from female rats and mice are better able to survive starvation than neurons from the males because they consume fat rather than protein, said researchers from the University of Pittsburgh School of Medicine, which could have implications for the nourishment of critically ill patients.

A team led by Robert Clark, M.D., associate professor of critical care medicine at Pitt, associate director of molecular biology at the Safar Center for Resuscitation Research and a pediatric intensivist at Children’s Hospital of Pittsburgh of UPMC, and Lina Du, M.D., research associate in the Department of Critical Care Medicine, cultured sets of neurons from male and female rats and mice, and deprived them of nutrients for 72 hours to gauge the potential impact of starvation on the brain.

“Within 24 hours, neurons from the males were dying off because they initiated a self-eating process called autophagy,” Dr. Clark said. “But neurons from the females mobilized fatty acids and made lipid droplets to use as a fuel source, prolonging their survival.”

The findings, published in the Jan. 23 issue of the Journal of Biological Chemistry, are the first indication that critical nutritional stress can kill neurons. Known to happen in other tissues during periods of starvation, possibly as a last-ditch survival effort, the process of autophagy leads to cell destruction and the breakdown of complex proteins, generating amino acids and other biological building blocks that could nourish remaining cells.

Sex differences in response to famine have been apparent for nearly a century, with females the heartier of the sexes. Part of the explanation for this observation could be that during nutritional deprivation, male cells tend to lean on energy primarily from protein sources, while female ones lean on fat. The current research suggests that during times of critical nutritional stress, males might be better off if they used fat-derived fuel as females do.

Autophagy-induced cell death in the brain could result in permanent damage, Dr. Clark said. Other research has revealed brain atrophy, or shrinkage, on scans of brain-injured and other critically ill patients, who likely were stressed and possibly insufficiently nourished during long hospitalizations.

“We really need to take critical care nutrition to the next level,” he said. “We can show that undernourishment of the brain during times of illness could lead to worse neurological outcomes, so it may be important to feed men and women, and boys and girls, differently to prevent brain cell death.”

Intensive care specialists are able to save more lives than ever before, noted study co-author and Safar Center director Patrick Kochanek, M.D., a vice chairman and professor of critical care medicine at Pitt’s School of Medicine.

“Prevention of subtle neurological problems, such as mild cognitive disturbances, is becoming a key final frontier in the intensive care unit,” he said. “Many times when these problems arise, the cause is somewhat of a mystery.”

In future work, Dr. Clark and his team hope to develop a bedside test to determine if the autophagy process is occurring in the brains of critically ill patients.

The research was supported by grants from the National Institutes of Health.

The University of Pittsburgh School of Medicine is one of the nation’s leading medical schools, renowned for its curriculum that emphasizes both the science and humanity of medicine and its remarkable growth in National Institutes of Health (NIH) grant support, which has more than doubled since 1998. For fiscal year 2006, the University ranked sixth out of more than 3,000 entities receiving NIH support with respect to the research grants awarded to its faculty. As one of the university’s six Schools of the Health Sciences, the School of Medicine is the academic partner to the University of Pittsburgh Medical Center (UPMC). Their combined mission is to train tomorrow’s health care specialists and biomedical scientists, engage in groundbreaking research that will advance understanding of the causes and treatments of disease and participate in the delivery of outstanding patient care.

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