Short Photoperiod-Induced Decrease of Histamine H3 Receptors Facilitates Activation of Hypothalamic Neurons in the Siberian Hamster

Short Photoperiod-Induced Decrease of Histamine H3 Receptors Facilitates Activation of Hypothalamic Neurons in the Siberian Hamster
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DOI:
10.1210/en.2008-1620
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发表时间:
2009-08-01
期刊:
影响因子:
4.8
通讯作者:
Spanswick, D.
Spanswick, D.
中科院分区:
医学2区
文献类型:
--
作者:
Barrett, P.;van den Top, M.;Spanswick, D.

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非冬眠的季节性哺乳动物通过行为和生理机制适应了食物供应的时间变化,在可预测的充足时期储存食物和能量,并在可预测的短缺期间保存能量。然而,我们对导致行为或生理变化的下丘脑神经元事件知之甚少。在这里,我们首次表明,从类似夏季的长光周期到类似冬季的短光周期的转变,导致西伯利亚仓鼠对冬季的生理适应,包括体重减轻高达 30%,通过电生理膜片钳记录评估,增加了弓状核背内侧区域 (dmpARC) 的神经元活动。短日内神经元活动的增加取决于光周期驱动的 H3 受体表达下调,并且可以通过应用 H3 受体拮抗剂 cloben-proprit 在长日照 dmpARC 神经元中进行模拟。 dmpARC 神经元的短日激活导致 c-Fos 表达增加。使用跨突触逆行示踪剂(伪狂犬病病毒)递送到脂肪组织中进行的纤维束追踪显示,多突触神经元交感神经从 dmpARC 流出到白色脂肪组织。这些数据强烈表明,组胺 H3 受体下调导致 dmpARC 神经元活性增加,有助于季节性光周期体重调节的生理适应。 (内分泌学 150:3655-3663,2009)
Nonhibernating seasonal mammals have adapted to temporal changes in food availability through behavioral and physiological mechanisms to store food and energy during times of predictable plenty and conserve energy during predicted shortage. Little is known, however, of the hypothalamic neuronal events that lead to a change in behavior or physiology. Here we show for the first time that a shift from long summer-like to short winter-like photoperiod, which induces physiological adaptation to winter in the Siberian hamster, including a body weight decrease of up to 30%, increases neuronal activity in the dorsomedial region of the arcuate nucleus (dmpARC) assessed by electrophysiological patch-clamping recording. Increased neuronal activity in short days is dependent on a photoperiod-driven down-regulation of H3 receptor expression and can be mimicked in long-day dmpARC neurons by the application of the H3 receptor antagonist, cloben-proprit. Short-day activation of dmpARC neurons results in increased c-Fos expression. Tract tracing with the trans-synaptic retrograde tracer, pseudorabies virus, delivered into adipose tissue reveals a multisynaptic neuronal sympathetic outflow from dmpARC to white adipose tissue. These data strongly suggest that increased activity of dmpARC neurons, as a consequence of down-regulation of the histamine H3 receptor, contributes to the physiological adaptation of body weight regulation in seasonal photoperiod. (Endocrinology 150: 3655-3663, 2009)