Scientists at the National Institutes of Health (NIH) have discovered a cellular mechanism in hibernating ground squirrels that may protect the nervous system from being damaged during extreme cold and lowered body temperatures, called hypothermia. This discovery could lead to a better understanding of the cellular mechanisms of hibernation and the cellular effects of hypothermia in non-hibernating animals. The communication appears in the September 21, 2000, issue of Nature (1).
Hibernation is a survival strategy that some mammals use during the winter to cope with shortages of food supplies and cold temperatures. When a mammal prepares for hibernation, its body temperature lowers to near-freezing temperature. For brief periods, the hibernating mammal will wake up and re-warm to normal body temperature before descending again into a state of lowered body temperature and hibernation. Somehow all the organs of the hibernating animal, including the central nervous system, survive these rapid temperature shifts without damage. Previous studies of cold adaptation during hibernation focused on cellular changes seen during the step-wise progression into hibernation, brought on by seasonal changes. This is one of the first studies to observe the cellular effects that accompany the rapid changes in body temperature occurring during deep hibernation.
"This study shows a physical membrane change through which cells may acclimate to extreme cold and still function," says John M. Hallenbeck, M.D., one of the authors and Chief of the Stroke Branch of the National Institute of Neurological Disorders and Stroke (NINDS).
The NIH scientists used light microscopy and freeze-fracture electron microscopy to examine the tissues of ground squirrels sampled during hibernation while in a hypothermic state and during arousal at room temperature. They discovered "slits" on microscopy images of the hibernating squirrels’ neurons and glia, the primary cells of the central nervous system. These slits correlated with patches of internal cell membrane devoid of protein, something that was not seen seen on images of non-hypothermic tissues.
The internal cell membrane studied is called the endoplasmic reticulum (ER), a highly folded membrane within the cell consisting of proteins and carbohydrates suspended in layers of lipids made up of saturated and unsaturated fatty acids. The purpose of the ER in the cell is to assist in the production of proteins, lipids, and other elements needed for cell metabolism. The saturated fatty acids of the membrane are like bacon grease in a refrigerator. When it gets cold, the grease freezes and turns solid. The unsaturated fatty acids are like olive oil, which remains liquid even in cold temperatures.
The scientists concluded that when squirrels’ body temperatures dropped to near freezing levels, the lipids and proteins in the membrane rearranged to form protein-free and protein-filled membrane areas. This mechanism allows proteins, the work-horses of the cell, the possibility to function within selected lipid domains in the membrane. If proteins stayed in the hardened area of the membrane, they would be frozen and unable to function, thereby compromising the activity of the cell, possibly to the point of cell death. By moving proteins to the fluid part of the ER membrane during times of low temperatures, the cell can continue to function and survive.
"These membrane changes, which result from the expected physical behavior of the lipids, rather than being deleterious, seem to form a membrane fluidity buffer and participate in the cellular mechanism of temperature acclimation,"says author Bechara Kachar, M.D., Chief of the Section on Structural Cell Biology of the National Institute on Deafness and Other Communication Disorders (NIDCD).
The NINDS, part of the National Institutes of Health in Bethesda, Maryland, is the nation’s leading supporter of research on the brain and nervous system. The NINDS is now celebrating its 50th anniversary.
NIDCD, also an institute of the NIH, supports and conducts basic and clinical research on normal and disordered processes of human communication.
(1)Azzam, Nabil A., John M. Hallenbeck, and Bechara Kachar. "Membrane changes during hibernation." Nature, Vol. 407, September 21, 2000, pp. 317-318.
Journal
Nature