Metabolic suppression in mammalian hibernation - Mechanisms and implications

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Through my research I aim to understand how hibernators survive cold prairie winters without eating. In the cold most small mammals increase metabolic heat production by shivering or activating brown adipose tissue. This strategy keeps body temperatures high and constant, but requires a great deal of food to power the high metabolic rates. By contrast hibernators allow their body temperature to fall close to freezing, and metabolic rate to decrease by over 90%. This strategy conserves energy over the winter when food is scarce. In 13-lined ground squirrels we discovered that the activity of mitochondria - cellular structures that consume oxygen to produce chemical energy and generate heat - is rapidly reduced by 70% during hibernation. This reduction corresponds with specific alterations to mitochondrial proteins, and we were able to reverse these changes in the lab. We will continue to explore what other protein alterations also occur. In addition, we will measure levels of hydrogen sulphide (H2S), and the enzymes that synthesize it, in hibernating ground squirrels. In large doses H2S is toxic, but some animal tissues actually synthesize it, and it may be important for regulating mitochondrial metabolism. This research will be valuable to biologists, but may also be important for developing techniques to prolong the viability of tissues used for transplantation In hibernation heart rate falls from 300 to 2 beats/minute and blood flow to many tissues virtually halts. Ground squirrels do not hibernate continuously throughout the winter, but arouse approximately every 12 days, increasing heart rate, metabolism and body temperature for approximately 18 hours. The decrease in heart rate followed by an abrupt increase is similar to what occurs in heart attack or stroke, and can produce a burst of reactive oxygen species which damage tissues. Ground squirrels are inherently resistant to this loss of blood flow, especially in the winter hibernation season. We predict that ground squirrel mitochondria produce fewer reactive oxygen species or have superior antioxidant defenses when they hibernate. Understanding how these animals cope with oxidative stress under natural conditions may help improve therapies for treating similar pathological conditions. Our ground squirrels are from Manitoba but this species ranges from Saskatchewan to Texas, and we do not know if hibernation patterns differ over this 20° latitudinal span. We will trap animals from 5 locations across this range, house them under identical, constant conditions and compare hibernation patterns. We will then use molecular biology to identify genetic markers that correspond with differences in hibernation patterns among populations. This approach may allow us to identify genes that regulate hibernation and inform us about how climate change may affect hibernators.