Neuropeptide Y suppresses thermogenic and cardiovascular sympathetic nerve activity via Y1 receptors in the paraventricular nucleus and dorsomedial hypothalamus.
Neuropeptide Y suppresses thermogenic and cardiovascular sympathetic nerve activity via Y1 receptors in the paraventricular nucleus and dorsomedial hypothalamus.
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DOI：
10.1111/jne.13006
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发表时间：
2021-08
影响因子：
3.2
通讯作者：
Brooks VL
中科院分区：
文献类型：
--
作者：
Shi Z;Bonillas AC;Wong J;Padilla SL;Brooks VL
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。在此，我们在麻醉的雄性大鼠中研究了外源性和内源性NPY通过与下丘脑室旁核（PVN）和背内侧下丘脑（DMH）中的Y1受体（NPY1R）结合对BAT SNA的抑制作用。使用雄性npy1r - cre小鼠以及在DMH或PVN单侧局部注射腺相关病毒（AAV）来鉴定表达PVN / DMH NPY1R的神经元的下游投射，腺相关病毒可使含NPY1R的神经元的细胞体、轴突纤维和神经末梢中依赖cre表达荧光蛋白（mCherry）。在寒冷大鼠的DMH中微量注射NPY可降低BAT SNA以及平均动脉压（MAP）和心率（HR），并且这些反应可被随后注射的选择性NPY1R拮抗剂BIBO3304逆转。在温暖的大鼠中，BAT SNA很少或没有，在DMH或PVN双侧微量注射BIBO3304可增加BAT SNA、MAP和HR。表达DMH NPY1R的神经元大量投射到苍白核（RPa）（此处有BAT交感神经节前神经元）以及PVN。在麻醉的小鼠中，DMH注射BIBO3304可增加内脏交感神经活动（SNA）、MAP和HR，所有这些都可被用荷包牡丹碱对PVN进行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去抑制作用。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中持续释放的NPY通过Y1R抑制BAT SNA、MAP和HR。BAT SNA的下游神经通路可能利用到RPa的直接投射。解除对BAT SNA的持续性NPY抑制可能有助于进食和饮食诱导的产热。
在DMH和PVN中持续释放的NPY通过Y1受体和可能利用到RPa直接投射的神经通路抑制BAT SNA。这种持续性NPY抑制的解除可能有助于进食和饮食诱导的产热。
In hungry animals, Neuropeptide Y (NPY) neurons 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. Here, 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 anesthetized male rats. Downstream projections of PVN/DMH NPY1R-expressing neurons were identified using male npy1r-cre mice and localized unilateral DMH or PVN injections of an adeno-associated virus (AAV), which allows for the cre-dependent expression of a fluorescent protein (mCherry) in the cell bodies, axon fibers, and nerve terminals of NPY1R-containing neurons. 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 neurons projected heavily to the Raphe Pallidus (RPa), which houses BAT presympathetic neurons, as well as the PVN. In anesthetized 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 neurons 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 utilize direct projections to the RPa. Release of tonic NPY inhibition of BAT SNA may contribute to feeding- and diet-induced thermogenesis. NPY tonically released in the DMH and PVN suppresses BAT SNA via Y1 receptors and neuropathways that may utilize direct projections to the RPa. Release of this tonic NPY inhibition may contribute to feeding- and diet-induced thermogenesis.
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DOI：
10.1523/jneurosci.4267-08.2009
发表时间：
2009-01-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Li AJ;Wang Q;Dinh TT;Ritter S
通讯作者：
Ritter S
影响因子：
2.9
作者：
Bi S
通讯作者：
Bi S
影响因子：
3.3
作者：
Oldfield, BJ;Giles, ME;McKinley, MJ
通讯作者：
McKinley, MJ
影响因子：
15.9
作者：
Krashes, Michael J.;Koda, Shuichi;Lowell, Bradford B.
通讯作者：
Lowell, Bradford B.
食物的感官检测快速调节弧形喂食电路。
影响因子：
64.5
作者：
Chen Y;Lin YC;Kuo TW;Knight ZA
通讯作者：
Knight ZA