Direct exposure to mild heat promotes proliferation and neuronal differentiation of neural stem/progenitor cells in vitro.
Direct exposure to mild heat promotes proliferation and neuronal differentiation of neural stem/progenitor cells in vitro.
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DOI：
10.1371/journal.pone.0190356
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Shido O
中科院分区：
文献类型：
--
作者：
Hossain ME;Matsuzaki K;Katakura M;Sugimoto N;Mamun AA;Islam R;Hashimoto M;Shido O
大鼠的热习服与下丘脑温度调节中心神经发生的增强有关。为了阐明热习服的机制，我们研究了直接温和热暴露对神经干细胞/祖细胞(NSCs/NPC)增殖和分化的影响。从14.5d胎鼠前脑皮质分离出神经干细胞/神经前体细胞，在37.0℃(对照组)和38.5℃(轻度热暴露)条件下培养4d，通过MTS细胞活力测定、神经球直径测量和细胞总数计数等方法研究其对细胞增殖的影响。采用实时定量聚合酶链式反应(Real Time PCR)、Western blotting和CM-H_2DCFDA法分别检测热休克蛋白(HSPs)和脑源性神经营养因子(BDNF)的mRNA表达、cAMP反应元件结合蛋白(CREB)和Akt磷酸化水平以及细胞内活性氧(ROS)水平。增殖条件下的热暴露增加了NSC/NPC的存活率、神经球直径和细胞计数。热暴露后BDNF mRNA表达、CREB磷酸化和ROS水平也明显升高。热暴露增加HSP27mRNA的表达，并伴随p-Akt水平的升高。此外，PI3K抑制剂LY294002可阻断热暴露对NSC/NPC增殖的影响。此外，分化条件下的热暴露增加了Tuj1(一种神经元标志物)阳性细胞的比例。这些发现表明，温和的热暴露可能通过激活Akt通路增加NSC/NPC的增殖，并促进神经元分化。温度对神经干细胞/神经前体细胞的直接影响可能是热习服大鼠下丘脑神经发生的机制之一。这种热诱导的神经再生也可能是治疗神经退行性疾病的有效策略。
Heat acclimation in rats is associated with enhanced neurogenesis in thermoregulatory centers of the hypothalamus. To elucidate the mechanisms for heat acclimation, we investigated the effects of direct mild heat exposure on the proliferation and differentiation of neural stem/progenitor cells (NSCs/NPCs). The NSCs/NPCs isolated from forebrain cortices of 14.5-day-old rat fetuses were propagated as neurospheres at either 37.0°C (control) or 38.5°C (mild heat exposure) for four days, and the effects on proliferation were investigated by MTS cell viability assay, measurement of neurosphere diameter, and counting the total number of cells. The mRNA expressions of heat shock proteins (HSPs) and brain-derived neurotrophic factor (BDNF), cAMP response element-binding (CREB) protein and Akt phosphorylation levels, and intracellular reactive oxygen species (ROS) levels were analyzed using real time PCR, Western blotting and CM-H2DCFDA assay respectively. Heat exposure under proliferation condition increased NSC/NPC viability, neurosphere diameter, and cell count. BDNF mRNA expression, CREB phosphorylation, and ROS level were also increased by heat exposure. Heat exposure increased HSP27 mRNA expression concomitant with enhanced p-Akt level. Moreover, treatment with LY294002 (a PI3K inhibitor) abolished the effects of heat exposure on NSC/NPC proliferation. Furthermore, heat exposure under differentiation conditions increased the proportion of cells positive for Tuj1 (a neuronal marker). These findings suggest that mild heat exposure increases NSC/NPC proliferation, possibly through activation of the Akt pathway, and also enhances neuronal differentiation. Direct effects of temperature on NSCs/NPCs may be one of the mechanisms involved in hypothalamic neurogenesis in heat-acclimated rats. Such heat-induced neurogenesis could also be an effective therapeutic strategy for neurodegenerative diseases.
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影响因子：
3.5
作者：
Konishi, H;Matsuzaki, H;Kikkawa, U
通讯作者：
Kikkawa, U
影响因子：
11.4
作者：
Jäättelä, M;Wissing, D;Egeblad, M
通讯作者：
Egeblad, M
影响因子：
2.7
作者：
Kikusato, Motoi;Yoshida, Hayami;Toyomizu, Masaaki
通讯作者：
Toyomizu, Masaaki
DOI：
10.1006/bbrc.2000.3805
发表时间：
2000-11-19
影响因子：
3.1
作者：
Bang, OS;Ha, BG;Kang, SS
通讯作者：
Kang, SS
DOI：
10.1615/critreveukargeneexpr.v18.i1.30
发表时间：
2008-01-01
影响因子：
1.6
作者：
Blanchetot, Christophe;Boonstra, Johannes
通讯作者：
Boonstra, Johannes