Different populations of prostaglandin EP3 receptor-expressing preoptic neurons project to two fever-mediating sympathoexcitatory brain regions.
Different populations of prostaglandin EP3 receptor-expressing preoptic neurons project to two fever-mediating sympathoexcitatory brain regions.
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DOI：
10.1016/j.neuroscience.2009.03.041
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发表时间：
2009-06-30
期刊：
影响因子：
3.3
通讯作者：
Morrison SF
中科院分区：
文献类型：
--
作者：
Nakamura Y;Nakamura K;Morrison SF
发热诱导的中枢机制由前列腺素E2（PGE 2）通过前列腺素E受体的EP 3亚型对视前区（POA）中的神经元的作用触发。表达EP 3受体（EP 3R）的POA神经元直接投射到下丘脑背内侧核（DMH）和中缝苍白核（rRPa），这是控制体温调节效应物的关键部位。基于生理学研究结果，我们假设棕色脂肪组织（BAT）和皮肤血管收缩剂中的发热反应是由单独的神经元通路独立控制的：PGE 2致热信号从表达EP 3R的POA神经元通过投射到DMH来激活BAT产热，并通过另一投射到rRPa来增加皮肤血管收缩。在这种情况下，DMH投射神经元和rRPA投射神经元将构成POA中表达EP 3R的神经元组内的分离群体。在这里，我们寻求直接的解剖学证据来验证这一假设与双示踪实验中，两种类型的逆行示踪剂，霍乱毒素b-亚基（CTb），共轭不同的荧光团被注射到DMH和大鼠的rRPa和由此产生的逆行标记的人口EP 3R免疫反应神经元的POA进行了鉴定与共聚焦显微镜。我们发现大量的EP 3R免疫反应神经元在DMH投射和rRPA投射人口。然而，非常少的EP 3R免疫反应POA神经元标记的CTB从DMH和从rRPa，虽然大量的神经元，不为EP 3R免疫反应双标记的CTB。缺乏EP 3R表达神经元发送侧支DMH和rRPa表明，致热信号发送独立的这些尾侧大脑区域从POA和POA的这种致热输出反映不同的控制机制BAT产热和皮肤血管收缩的不同组的POA神经元。
The central mechanism of fever induction is triggered by an action of prostaglandin E2 (PGE2) on neurons in the preoptic area (POA) through the EP3 subtype of prostaglandin E receptor. EP3 receptor (EP3R)-expressing POA neurons project directly to the dorsomedial hypothalamus (DMH) and to the rostral raphe pallidus nucleus (rRPa), key sites for the control of thermoregulatory effectors. Based on physiological findings, we hypothesize that the febrile responses in brown adipose tissue (BAT) and those in cutaneous vasoconstrictors are controlled independently by separate neuronal pathways: PGE2 pyrogenic signaling is transmitted from EP3R-expressing POA neurons via a projection to the DMH to activate BAT thermogenesis and via another projection to the rRPa to increase cutaneous vasoconstriction. In this case, DMH-projecting and rRPa-projecting neurons would constitute segregated populations within the EP3R-expressing neuronal group in the POA. Here, we sought direct anatomical evidence to test this hypothesis with a double-tracing experiment in which two types of the retrograde tracer, cholera toxin b-subunit (CTb), conjugated with different fluorophores were injected into the DMH and the rRPa of rats and the resulting retrogradely labeled populations of EP3R-immunoreactive neurons in the POA were identified with confocal microscopy. We found substantial numbers of EP3R-immunoreactive neurons in both the DMH-projecting and the rRPa-projecting populations. However, very few EP3R-immunoreactive POA neurons were labeled with both the CTb from the DMH and that from the rRPa, although a substantial number of neurons that were not immunoreactive for EP3R were double-labeled with both CTbs. The paucity of the EP3R-expressing neurons that send collaterals to both the DMH and the rRPa suggests that pyrogenic signals are sent independently to these caudal brain regions from the POA and that such pyrogenic outputs from the POA reflect different control mechanisms for BAT thermogenesis and for cutaneous vasoconstriction by distinct sets of POA neurons.
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影响因子：
5.5
作者：
Nakamura, Kazuhiro;Morrison, Shaun F.
通讯作者：
Morrison, Shaun F.
影响因子：
3.3
作者：
Madden, CJ;Morrison, SF
通讯作者：
Morrison, SF
影响因子：
2.5
作者：
Nakamura, K;Kaneko, T;Negishi, M
通讯作者：
Negishi, M
影响因子：
5.5
作者：
BOULANT, JA;HARDY, JD
通讯作者：
HARDY, JD
DOI：
10.1152/ajpregu.00427.2006
发表时间：
2007-01-01
影响因子：
2.8
作者：
Nakamura, Kazuhiro;Morrison, Shaun F.
通讯作者：
Morrison, Shaun F.