Animals at the extremes: Hibernation and torpor

# 4.2 Arresting protein synthesis

The regulation of T b in hibernators has traditionally been viewed as the fundamental physiological process in hibernation. But recently, questions have been raised about whether thermal changes initiate or simply accompany metabolic depression. Is the metabolic inactivity of animal tissues during bouts of torpor or in hibernation, the cause or the result of hypothermia? A common-sense view is that temperature directly influences metabolism by regulating enzyme activity. Evidence of separate, temperature-independent regulation of metabolic processes in hibernators would lead us to reconsider the classical view of hibernation.

In greater horseshoe bats (Rhinolophus ferrumequinum), in which large changes both in T b and in body mass occur during hibernation, the duration of torpor is inversely related both to T a and to the animal's level of body hydration in hibernating ground squirrels. Protein synthesis in brain tissue is actively arrested for several weeks at a time and, at the onset of hibernation, mRNA is translated into protein at a much slower rate in brain tissue extracts even when measured at 37° C (Frerichs, 1998).

This change in metabolism may lead to the onset of cellular quiescence during hibernation. Protein synthesis in vivo, as measured by the incorporation of radioactive leucine into the brain tissue of ground squirrels, is almost undetectable during entry into hibernation, even though T b is still high. Figure 25a is an autoradiogram which shows tissue sections that have been exposed for several days to X-ray film. The colours represent different levels of incorporation that are detected as radioactive emissions. The green areas show relatively high levels of incorporation in an area of the brain called the hippocampus in the active but not in the hibernating animal. The in vitro studies in Figure 25b confirm that there is relatively little leucine incorporation into the brain tissue of the hibernating animal. The differences in control mechanisms over protein synthesis in hibernating and euthermic brains are subtle. There is no difference in the structure or quantity of mRNA or the functioning of the ribosomes on which it is translated to protein. However the ‘transit time’, or duration taken for polyribosomes to process each mRNA molecule, is three times longer in hibernating animals. The initiation factor, eIF2, which is involved in the aggregation of ribosomes and the initiation of translation, may be inhibited in hibernating cells. Although this finding does not point to suppression of specific areas of metabolism, we can predict that energy generation, tissue homeostasis and growth are all likely to be suppressed by a general fall in protein synthesis.

Figure 25 Suppression of protein synthesis in brain...
Suppression of protein synthesis in brain...
Frerichs, K. U. and Smith, C. B. et al. (1998) Suppression of protein synthesis in brain…, Proceedings of the National Academy of Sciences, 95. National Academy of Sciences

## Figure 25a, b Discussion

Figure 25a contains colour-coded autoradiograms, showing rates of cerebral protein synthesis as detected by the incorporation of a radioactive derivative of leucine in an active (left) and a hibernating (right) ground squirrel in coronal (vertical and left-to-right) sections of the brain at the level of the hypothalamus. The bar on the right of each figure shows increasing levels of leucine incorporation from purple (zero) to red (high). During hibernation, leucine incorporation was not detected. FIgure 25b shows that cytoplasm from hibernating cells translates mRNA to protein at a lower rate than euthermic cells, even at 37° C. Following introduction of radio-labelled leucine at time zero, the reaction was allowed to proceed for 30 minutes. Incorporation of leucine into the cell extract was several times higher in cells from active (left) compared with those from hibernating (right) brains. Incorporation was blocked by cycloheximide (+CHX), a specific inhibitor of protein synthesis.

However, the change in protein synthesis in laboratory experiments is just as evident in cells from hibernating animals at 37° C; it does not appear to be a consequence of thermoregulation. This finding does not mean that the change from protein synthesis is wholly independent of thermoregulation. In golden-mantled ground squirrels, reorganization of polysomes and an increase in mRNA elongation increases abruptly at 18° C during arousal, as the need for protein synthesis becomes critical.

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