Mild hypothermia facilitates the expression of cold-inducible RNA-binding protein and heat shock protein 70.1 in mouse brain

An appropriate thermal control system is essential for maintaining brain homeostasis. Hypothermia is a decrease in core body temperature that occurs when the thermoregulatory responses of homeotherrnic animals are impaired by environmental and situational influences, such as cold ambience and anesthesia. In recent years, hypothermia has been used for medical treatment, i.e., therapeutic hypothermia, for patients with stroke, traumatic brain injury, and heart surgery. However, the target molecules acting during hypothermia have not been identified. To understand the molecular mechanisms, we generated a mouse model of mild hypothermia (1 degrees C-2 degrees C below normal), and analyzed the expression of several genes. After mice were exposed to cold for 24 and 48 h, their rectal temperature reached 33 degrees C-35 degrees C. Then, using real-time quantitative PCR, we analyzed the mRNA expression levels of c-fos, cold-inducible RNAbinding protein (CIRP), heat shock protein (hsp) 70.1, oxytocin, and representative inflammatory cytokines, i.e., tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in target organs. Importantly, we found that the expression levels of CIRP and hsp70.1 were elevated in the olfactory bulb within 48 h. In the hypothalamus, CIRP expression levels increased and were followed by an increase in hsp70.1 expression. Meanwhile, TNF-alpha and IL-6 expression decreased gradually over 24 and 48 h in the olfactory bulb and hypothalamus. These specific expression profiles, i.e., enhanced CIRP and hsp70.1 expression and depressed cytokine expression, suggest that they could regulate apoptosis related to the cytokine signaling. (c) 2012 Elsevier B.V. All rights reserved.