Neuropeptide Y suppresses thermogenic and cardiovascular sympathetic nerve activity via Y1 receptors in the paraventricular nucleus and dorsomedial hypothalamus,Journal of Neuroendocrinology

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Neuropeptide Y suppresses thermogenic and cardiovascular sympathetic nerve activity via Y1 receptors in the paraventricular nucleus and dorsomedial hypothalamus
Journal of Neuroendocrinology ( IF 3.3 ) Pub Date : 2021-06-21 , DOI: 10.1111/jne.13006
Zhigang Shi ₁ , Alyssa C Bonillas ₁ , Jennifer Wong ₁ , Stephanie L Padilla ₂ , Virginia L Brooks ₁

Affiliation

In hungry animals, neuropeptide Y (NPY) neurones in the arcuate nucleus (ArcN) are activated to suppress energy expenditure, in part by decreasing brown adipose tissue sympathetic nerve activity (BAT SNA); however, the NPY receptor subtype and brain neurocircuitry are unclear. In the present study, we investigated the inhibition of BAT SNA by exogenous and endogenous NPY via binding to Y1 receptors (NPY1R) in the hypothalamic paraventricular nucleus (PVN) and dorsomedial hypothalamus (DMH), in anaesthetised male rats. Downstream projections of PVN/DMH NPY1R-expressing neurones were identified using male Npy1r-cre mice and localised unilateral DMH or PVN injections of an adeno-associated virus, which allows for the cre-dependent expression of a fluorescent protein (mCherry) in the cell bodies, axon fibres and nerve terminals of NPY1R-containing neurones. Nanoinjections of NPY into the DMH of cooled rats decreased BAT SNA, as well as mean arterial pressure (MAP) and heart rate (HR), and these responses were reversed by subsequent injection of the selective NPY1R antagonist, BIBO3304. In warmed rats, with little to no BAT SNA, bilateral nanoinjections of BIBO3304 into the DMH or PVN increased BAT SNA, MAP and HR. DMH NPY1R-expressing neurones projected heavily to the raphe pallidus (RPa), which houses BAT presympathetic neurones, as well as the PVN. In anaesthetised mice, DMH BIBO3304 increased splanchnic SNA, MAP and HR, all of which were reversed by nonselective blockade of the PVN with muscimol, suggesting that DMH-to-PVN connections are involved in this DMH BIBO3304 disinhibition. PVN Y1R expressing neurones also projected to the RPa, as well as to the nucleus tractus solitarius. We conclude that NPY tonically released in the DMH and PVN suppresses BAT SNA, MAP and HR via Y1R. Downstream neuropathways for BAT SNA may utilise direct projections to the RPa. Release of tonic NPY inhibition of BAT SNA may contribute to feeding- and diet-induced thermogenesis.

中文翻译：

神经肽 Y 通过室旁核和下丘脑背内侧的 Y1 受体抑制产热和心血管交感神经活动

在饥饿的动物中，弓状核 (ArcN) 中的神经肽 Y (NPY) 神经元被激活以抑制能量消耗，部分是通过降低棕色脂肪组织的交感神经活动 (BAT SNA)；然而，NPY 受体亚型和脑神经回路尚不清楚。在本研究中，我们通过与麻醉雄性大鼠下丘脑室旁核 (PVN) 和下丘脑背内侧 (DMH) 中的 Y1 受体 (NPY1R) 结合，研究了外源性和内源性 NPY 对 BAT SNA 的抑制作用。使用雄性N py1r - cre鉴定了表达 PVN/DMH NPY1R 的神经元的下游预测小鼠和局部单侧 DMH 或 PVN 注射腺相关病毒，这允许荧光蛋白 (mCherry) 在含有 NPY1R 的神经元的细胞体、轴突纤维和神经末梢中依赖 cre 表达。将 NPY 纳米注射到冷却大鼠的 DMH 中可降低 BAT SNA、平均动脉压 (MAP) 和心率 (HR)，随后注射选择性 NPY1R 拮抗剂 BIBO3304 可逆转这些反应。在温暖的大鼠中，几乎没有或没有 BAT SNA，将 BIBO3304 双侧纳米注射到 DMH 或 PVN 增加了 BAT SNA、MAP 和 HR。表达 DMH NPY1R 的神经元大量投射到苍白中缝 (RPa)，其中包含 BAT 前交感神经元，以及 PVN。在麻醉小鼠中，DMH BIBO3304 增加内脏 SNA、MAP 和 HR，所有这些都被 muscimol 对 PVN 的非选择性阻断所逆转，这表明 DMH 到 PVN 的连接参与了这种 DMH BIBO3304 去抑制。表达 PVN Y1R 的神经元也投射到 RPa 以及孤束核。我们得出结论，在 DMH 和 PVN 中释放的 NPY 通过 Y1R 抑制 BAT SNA、MAP 和 HR。BAT SNA 的下游神经通路可以利用对 RPa 的直接投射。释放 BAT SNA 的补品 NPY 抑制可能有助于喂养和饮食诱导的产热。MAP 和 HR 通过 Y1R。BAT SNA 的下游神经通路可以利用对 RPa 的直接投射。释放 BAT SNA 的补品 NPY 抑制可能有助于喂养和饮食诱导的产热。MAP 和 HR 通过 Y1R。BAT SNA 的下游神经通路可以利用对 RPa 的直接投射。释放 BAT SNA 的补品 NPY 抑制可能有助于喂养和饮食诱导的产热。

更新日期：2021-08-25

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