Origin of thyrotropin-releasing hormone neurons that innervate the tuberomammillary nuclei.

Origin of thyrotropin-releasing hormone neurons that innervate the tuberomammillary nuclei.
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DOI:
10.1007/s00429-022-02527-5
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发表时间:
2022-09
影响因子:
3.1
通讯作者:
Lechan, Ronald M.
Lechan, Ronald M.
中科院分区:
医学3区
文献类型:
--
作者:
Sanchez-Jaramillo, Edith;Wittmann, Gabor;Menyhert, Judit;Singru, Praful;Gomez-Gonzalez, Gabriela B.;Sanchez-Islas, Eduardo;Yanez-Recendis, Nashiely;Arturo Pimentel-Cabrera, Jaime;Leon-Olea, Martha;Gereben, Balazs;Fekete, Csaba;Charli, Jean-Louis;Lechan, Ronald M.

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促甲状腺激素释放激素(TRH)神经元作为代谢感受器调节甲状腺轴和能量平衡。对下丘脑其他TRH神经元的作用知之甚少。由于中枢应用TRH减少了食物的摄取,增加了结节乳头核(TMN)中的组胺,并且TMN组胺神经元被未知来源的TRH纤维密集支配,我们定位了投射到TMN的TRH神经元的位置。将霍乱毒素B亚单位(CTB)逆行示踪剂注入成年SD雄性大鼠TMN的E_1~E_2、E_4~E_5区。TMN投射神经元分布于隔核、视前区、终纹床核、穹隆周区、室旁前核、下丘脑脚和结节外侧核、视交叉上核和杏仁内侧核。而CTB/PRO-TRH178-199双标细胞仅见于TuLH区。将顺行示踪剂菜豆亮氨酸凝集素(PHAL)注入TuLH区,证实了逆行示踪结果的特异性。双标记的PHAL-PRO-TRH启动子存在于TMN的所有亚区。TMN神经元的组氨酸脱羧酶(HDC)/PHAL、HDC/TRH受体(TRHR)和HDC/TRH双标。在显微注射表达mCherry的Cre重组酶依赖的AAV后,在一只在TRH产生细胞中表达CRE重组酶的转基因小鼠中,进一步证实了TuLH-TRH神经元向TMN的投射。我们认为,在啮齿类动物中,TMN的TRH神经支配部分来源于TuLH内的TRH神经元,这种TRH群可能通过TMN的组胺TRHR阳性神经元来调节能量平衡。网上版载有补充材料,可在10.1007/s00429-022-02527-5查阅。
Hypophysiotropic thyrotropin-releasing hormone (TRH) neurons function as metabolic sensors that regulate the thyroid axis and energy homeostasis. Less is known about the role of other hypothalamic TRH neurons. As central administration of TRH decreases food intake and increases histamine in the tuberomammillary nuclei (TMN), and TMN histamine neurons are densely innervated by TRH fibers from an unknown origin, we mapped the location of TRH neurons that project to the TMN. The retrograde tracer, cholera toxin B subunit (CTB), was injected into the TMN E1–E2, E4–E5 subdivisions of adult Sprague–Dawley male rats. TMN projecting neurons were observed in the septum, preoptic area, bed nucleus of the stria terminalis (BNST), perifornical area, anterior paraventricular nucleus, peduncular and tuberal lateral hypothalamus (TuLH), suprachiasmatic nucleus and medial amygdala. However, CTB/pro-TRH178-199 double-labeled cells were only found in the TuLH. The specificity of the retrograde tract-tracing result was confirmed by administering the anterograde tracer, Phaseolus vulgaris leuco-agglutinin (PHAL) into the TuLH. Double-labeled PHAL-pro-TRH boutons were identified in all subdivisions of the TMN. TMN neurons double-labeled for histidine decarboxylase (Hdc)/PHAL, Hdc/Trh receptor (Trhr), and Hdc/Trh. Further confirmation of a TuLH-TRH neuronal projection to the TMN was established in a transgenic mouse that expresses Cre recombinase in TRH-producing cells following microinjection of a Cre recombinase-dependent AAV that expresses mCherry into the TuLH. We conclude that, in rodents, the TRH innervation of TMN originates in part from TRH neurons in the TuLH, and that this TRH population may contribute to regulate energy homeostasis through histamine Trhr-positive neurons of the TMN. The online version contains supplementary material available at 10.1007/s00429-022-02527-5.
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