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Effect of glucocorticoid depletion on heat-induced Hsp70, IL-1beta and TNF-alpha gene expression.

Abstract : When exposed to heat, conscious naive rats may develop lethal heatstroke, depending on heat load, i.e., time spent at high body core temperature. The occurrence of heatstroke was hypothesized to result from a defective glucocorticoid secretion related to altered heat-stress responses. We thus investigated the potential involvement of glucocorticoids in heat tolerance and its consequences on physiological responses, heat shock protein 70 (Hsp70), and cytokine mRNA expressions. Two hours before heat exposure, the animals were injected either with metyrapone, an inhibitor of corticosterone synthesis, or with its vehicle. Heat exposure lasted for 15, 30, 45 or 60 min. Thereafter, the rats were distributed into three groups according to their heat load: null, moderate (without any lethal risk) and intense (with lethal risk). Physiological responses were evaluated with colonic temperature, plasma lactate and hematocrit. Brain responses were assessed in frontal cortex through Hsp70, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) mRNA expressions. The animals with a severe heat load exhibited a high hematocrit, increased plasma lactate level and enhanced brain IL-1beta and Hsp70 mRNA expressions. Independent of the heat load, Metyrapone rats showed the same thermophysiological responses and IL-1beta and Hsp70 mRNA expressions when compared with vehicle rats. However, the Metyrapone rats experiencing an intense heat load exhibited an increased TNF-alpha mRNA expression. In conclusion, these data (i) confirm that heat load is important in the calibration of the risk attached to heat exposure; and (ii) suggest that corticosterone synthesis inhibition may favor TNF-alpha mRNA expression without any effect on Hsp70 mRNA expression.
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Contributor : Valérie Sinniger <>
Submitted on : Thursday, September 10, 2009 - 1:00:42 PM
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Virginie Michel, André Peinnequin, Antonia Alonso, Alain Buguet, Raymond Cespuglio, et al.. Effect of glucocorticoid depletion on heat-induced Hsp70, IL-1beta and TNF-alpha gene expression.. Brain Research, Elsevier, 2007, 1164, pp.63-71. ⟨10.1016/j.brainres.2007.06.011⟩. ⟨inserm-00388023⟩



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