Matsuzaki Kentaro, Katakura Masanori, Sugimoto Naotoshi, Hara Toshiko, Hashimoto Michio, Shido Osamu
Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumo, Japan.
Department of Nutritional Physiology, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
PLoS One. 2017 Jun 19;12(6):e0178787. doi: 10.1371/journal.pone.0178787. eCollection 2017.
Constant exposure to moderate heat facilitates progenitor cell proliferation and neuronal differentiation in the hypothalamus of heat-acclimated (HA) rats. In this study, we investigated neural phenotype and responsiveness to heat in HA rats' hypothalamic newborn cells. Additionally, the effect of hypothalamic neurogenesis on heat acclimation in rats was evaluated. Male Wistar rats (5 weeks old) were housed at an ambient temperature (Ta) of 32°C for 6 days (STHA) or 40 days (LTHA), while control (CN) rats were kept at a Ta of 24°C for 6 days (STCN) or 40 days (LTCN). Bromodeoxyuridine (BrdU) was intraperitoneally injected daily for five consecutive days (50 mg/kg/day) after commencing heat exposure. The number of hypothalamic BrdU-immunopositive (BrdU+) cells in STHA and LTHA rats was determined immunohistochemically in brain samples and found to be significantly greater than those in respective CN groups. In LTHA rats, approximately 32.6% of BrdU+ cells in the preoptic area (POA) of the anterior hypothalamus were stained by GAD67, a GABAergic neuron marker, and 15.2% of BrdU+ cells were stained by the glutamate transporter, a glutamatergic neuron marker. In addition, 63.2% of BrdU+ cells in the POA were immunolabeled with c-Fos. Intracerebral administration of the mitosis inhibitor, cytosine arabinoside (AraC), interfered with the proliferation of neural progenitor cells and acquired heat tolerance in LTHA rats, whereas the selected ambient temperature was not changed. These results demonstrate that heat exposure generates heat responsive neurons in the POA, suggesting a pivotal role in autonomic thermoregulation in long-term heat-acclimated rats.
持续暴露于适度高温可促进热适应（HA）大鼠下丘脑祖细胞增殖和神经元分化。在本研究中，我们调查了HA大鼠下丘脑新生细胞的神经表型及其对热的反应性。此外，还评估了下丘脑神经发生对大鼠热适应的影响。将雄性Wistar大鼠（5周龄）置于32°C环境温度（Ta）下6天（短期热适应，STHA）或40天（长期热适应，LTHA），而对照（CN）大鼠则置于24°C的Ta下6天（短期对照，STCN）或40天（长期对照，LTCN）。开始热暴露后，连续5天每天腹腔注射溴脱氧尿苷（BrdU）（50 mg/kg/天）。通过免疫组织化学方法测定STHA和LTHA大鼠下丘脑BrdU免疫阳性（BrdU+）细胞的数量，发现其显著多于各自的CN组。在LTHA大鼠中，下丘脑前部视前区（POA）约32.6%的BrdU+细胞被GABA能神经元标志物GAD67染色，15.2%的BrdU+细胞被谷氨酸能神经元标志物谷氨酸转运体染色。此外，POA中63.2%的BrdU+细胞被c-Fos免疫标记。脑内注射有丝分裂抑制剂阿糖胞苷（AraC）会干扰神经祖细胞的增殖，并影响LTHA大鼠获得耐热性，而选定的环境温度未改变。这些结果表明，热暴露可在POA中产生热反应性神经元，提示其在长期热适应大鼠的自主体温调节中起关键作用。
