Hypoxia reduces the hypothalamic thermogenic threshold and thermosensitivity

Hypoxia is well known to reduce the body temperature (T(b)) of mammals, although the neural origins of this response remain uncertain. Short-term hypoxic exposure causes a reduction in the lower critical temperature of the thermal neutral zone and a reduction in whole body thermal conductance of rodents, providing indirect support that hypoxia lowers T(b) in a regulated manner. In this study, we examined directly the potential for changes in central thermosensitivity to evoke the hypoxic metabolic response by heating and cooling the preoptic area of the hypothalamus (the area which integrates thermoreceptor input and regulates thermoeffector outputs) using chronic, indwelling thermodes in ground squirrels during normoxia and hypoxia (7, 10 and 12% O(2)). We found that the threshold hypothalamic temperature for the metabolic response to cooling (T(th)) of approximately 38 degrees C in normoxia was proportionately reduced in hypoxia (down to 28-31 degrees C at 7% O(2)) and that the metabolic thermosensitivity (alpha; the change in metabolic rate for any given change in hypothalamic temperature below the lower critical temperature) was comparatively reduced by 5 to 9 times. This provides strong support for the hypothesis that the fall in temperature that occurs during hypoxia is the result of a reduction in the activation of thermogenic mechanisms. The decrease in the central thermosensitivity in hypoxia, however, appears to be a critical factor in the alteration of mammalian T(b). We suggest, therefore, that an altered central thermosensitivity may provide a proximate explanation of how low oxygen and similar stressors reduce normal fluctuations in T(b) (i.e. circadian), in addition to the depression in regulated T(b).