Cooling‐activated dorsomedial hypothalamic BDNF neurons control cold defense in mice
Cooling‐activated dorsomedial hypothalamic BDNF neurons control cold defense in mice
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DOI：
10.1111/jnc.15666
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发表时间：
2022-07
影响因子：
4.7
通讯作者：
Qian Zhou;Changhao Liu;Ting Chen;Yanyang Liu;Ren Cao;Xinyan Ni;Wen Z. Yang;Qiwei Shen;
中科院分区：
文献类型：
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作者：
Qian Zhou;Changhao Liu;Ting Chen;Yanyang Liu;Ren Cao;Xinyan Ni;Wen Z. Yang;Qiwei Shen;
BDNF及其在大脑中的表达神经元关键地控制啮齿动物和人类的进食和能量消耗（EE）。然而，BDNF神经元在温度挑战期间是否在温度调节中起作用尚不清楚。在这里，我们表明，BDNF神经元在背内侧下丘脑（DMHBDNF）的小鼠被激活的传入冷却信号。这些冷却激活的BDNF神经元主要是GABA能的。DMHBDNF神经元或GABA能亚群的激活足以增加体温、EE和体力活动。相反，阻断DMHBDNF神经元实质上损害冷防御，并减少BAT中的能量消耗、体力活动和UCP 1表达，最终导致体重增加和葡萄糖/胰岛素耐受不良。因此，我们将DMHBDNF神经元的一个子集确定为一种新型的冷却激活神经元，以促进冷防御。因此，我们揭示了BDNF回路在体温调节中的关键作用，这加深了我们对BDNF在控制能量稳态和肥胖中的理解。
BDNF and its expressing neurons in the brain critically control feeding and energy expenditure (EE) in both rodents and humans. However, whether BDNF neurons would function in thermoregulation during temperature challenges is unclear. Here, we show that BDNF neurons in the dorsomedial hypothalamus (DMHBDNF) of mice are activated by afferent cooling signals. These cooling‐activated BDNF neurons are mainly GABAergic. Activation of DMHBDNF neurons or the GABAergic subpopulations is sufficient to increase body temperature, EE, and physical activity. Conversely, blocking DMHBDNF neurons substantially impairs cold defense and reduces energy expenditure, physical activity, and UCP1 expression in BAT, which eventually results in bodyweight gain and glucose/insulin intolerance. Therefore, we identify a subset of DMHBDNF neurons as a novel type of cooling‐activated neurons to promote cold defense. Thus, we reveal a critical role of BDNF circuitry in thermoregulation, which deepens our understanding of BDNF in controlling energy homeostasis and obesity.