Elena O. Gracheva
Molecular basis of reversible hypothermia in mammalian hibernators
Yale University School of Medicine
Cellular & Molecular Physiology/CNNR program
Hibernating mammals possess a unique ability to passively reduce their body temperature to ambient levels, which can be as low as 2°C. Despite such a depressed physiological phenotype, hibernators still maintain activity in their nervous system as evidenced by their continued sensitivity to auditory, tactile and thermal stimulation. The molecular mechanisms that underlie this adaptation remain unknown. Here, we found that torpid thirteen-lined ground squirrels (Ictidomys tridecemlineatus) keep their brain temperature significantly elevated above ambient and that of the rest of the body. Differential transcriptomics alongside immunohistological and biochemical analyses showed that squirrel neurons express mitochondrial uncoupling protein 1 (UCP1) during hibernation. Heterologously expressed squirrel UCP1 displays uncoupling properties consistent with the observed heat generation in squirrel brain. We propose that the expression of UCP1 in neuronal mitochondria provides a molecular mechanism for local thermogenesis in the nervous system during torpor.