A team of Pittsburgh scientists which included McGowan Institute for Regenerative Medicine
faculty members Charleen T. Chu, MD, PhD (top), Patrick M. Kochanek, MD (center), and Simon C. Watkins, PhD (bottom), recently reported that neurons from female rats and mice are better able to survive starvation than neurons from the males because they consume fat rather than protein. These study results could have implications for the nourishment of critically ill patients.
The group of researchers 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. In 24 hours there was a marked difference in neuron behavior. The neurons from the males began dying off due to an initiated self-eating process called autophagy. However the females mobilized fatty acids and made lipid droplets to use as a fuel source, thus enabling them to survive.
The findings 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. 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. Since undernourishment of the brain could lead to worse neurological outcomes, it may be important to feed the genders differently to prevent brain cell death.
Intensive care specialists are able to save more lives than ever before, noted Dr. Kochanek.
“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, the team hopes to develop a bedside test to determine if the autophagy process is occurring in the brains of critically ill patients.
Dr. Chu is an associate professor of Neuropathology, Pathology Department, with a secondary appointment in Opthalmology. Dr. Kochanek is the director, Safar Center for Resuscitation Research, and professor, Departments of Critical Care Medicine, Pediatrics, and Anesthesiology. Dr. Watkins is founder and director of the Center for Biologic Imaging, University of Pittsburgh, and professor, Department of Cell Biology and Physiology.
Illustration: McGowan Institute for Regenerative Medicine.
University of Pittsburgh Schools of the Health Sciences Media Relations News Release (01/23/09)
Health News Digest (01/23/09)
Bio: Dr. Charlene Chu
Bio: Dr. Patrick Kochanek
Bio: Dr. Simon Watkins
Abstract (Journal of Biological Chemistry, Vol. 284, Issue 4, 2383-2396, January 23, 2009)