Housing temperature influences the pattern of heat shock protein induction in mice following mild whole body hyperthermia

Abstract

Purpose Researchers studying the response of mice to stress generally use mice housed under standard, nationally-enforced conditions as controls. Few investigators are concerned whether basic, physical aspects of mouse housing could also be a source of stress, capable of influencing the subsequent impact of an experimentally applied stressor. We have recently become aware of the potential for standard housing conditions to influence important physiological and immunological properties in mice. Materials and Methods Here, we sought to determine whether housing mice at standard temperature (ST; 22°C) versus thermoneutral temperature (TT; 30°C) influences baseline expression of heat shock proteins (HSPs) and their typical induction following a whole body heating. Results There were not significant differences in baseline expression of HSPs at ST and TT. However, in several cases, we induction of HSP70, HSP110, and HSP90 in tissues of mice maintained at ST was greater than at ST, following 6 hours of heating which elevated core body temperature to 39.5°C. This loss of HSP induction was also obtained when mice housed at ST were given propranolol, a β-adrenergic receptor antagonist, used clinically to treat hypertension and stress. Conclusions Taken together, these data show that housing temperature has a significant influence on the expression of HSPs in mice after whole body heating and should be considered when stress responses are studied in mice.

Thermoneutrality, Mice, and Cancer: A Heated Opinion

“…The key to reproducibility is accurate reporting of these seemingly mundane details, which potentially have large effects ' [87]. Although housing temperature was not included as a factor in these analyses, studies are accumulating in which experimental outcomes differ depending on the ambient temperature; these are summarized in Figure 1 [7,10,11,19,27,28,40,42,44,46,48,63,66,67,70,79,84,[88][89][90][91][92][93][94] biomedical applications, and how this condition may influence decisions for translation to the clinic (see Outstanding Questions). It is likely that many, if not all, of the metabolic abnormalities noted previously in mouse models stem largely from chronic mild cold stress and the increase in adaptive thermogenesis.…”

“…Comparisons of BAT by MRI could also prove to be a valuable and relevant biomarker of the degree of cold-stress in experimental mice at different ambient temperatures [40]. Sleep [79,94 ] Obesity [63,66,67 [7,10,12,[27][28][29]37,40,[42][43][44]46,47,63,66,67,70,71,79,84,89,93,94]). Several other conditions or phenomena that are modeled in mice and are likely to be influenced by housing temperature, but for which there is little or no published information are also listed (followed by ?).…”

Temperature increases by kilohertz frequency spinal cord stimulation

“…Thus, kHz stimulation deposits more power in the tissue than conventional spinal cord stimulation and is therefore more likely to significantly heat the tissue immediately surrounding the stimulation site. A temperature increase and resultant thermal conduction into the spinal cord can, in turn, affect neuronal function 23 (e.g., via alteration of ion channel or neurotransmitters dynamics) and related biological functions (e.g., via vasodilation 24 , heat shock protein expression 25 ) depending on the degree of change. Tissue heating further encourages the expression of anti-inflammatory agents, such as heat shock proteins 26 , over a period of time consistent with the extended wash-in times of kHz-SCS treatment.…”

Housing temperature-induced stress drives therapeutic resistance in murine tumour models through β2-adrenergic receptor activation

“…We found that the standard temperature at which mice are housed impacts basic physiology and tumour progression in experimental mouse models. Specifically, the mildly cool, sub-thermoneutral housing temperature mandated at all research facilities 5 significantly alters both the heat shock protein expression in healthy mice and the anti-tumour immune response 6–8 . In comparison to mice housed at standard temperature (ST; 22 °C), growth of both syngeneic cell lines and carcinogen-induced tumours was significantly delayed in animals housed at thermoneutral temperatures (TT; 30 °C) 8 .…”