Mediobasal hypothalamic neurons contribute to the control of brown adipose tissue sympathetic nerve activity and cutaneous vasoconstriction.
Mediobasal hypothalamic neurons contribute to the control of brown adipose tissue sympathetic nerve activity and cutaneous vasoconstriction.
复制标题
下丘脑中部神经元有助于控制棕色脂肪组织交感神经活动和皮肤血管收缩。
DOI：
10.1016/j.jtherbio.2023.103551
复制
发表时间：
2023
影响因子：
2.7
通讯作者：
Madden,ChristopherJ
中科院分区：
文献类型：
--
作者：
Mota,ClarissaMD;Madden,ChristopherJ
中基底下丘脑（MBH）含有调节食物摄入和能量消耗的异质神经元群。然而，MBH神经元在热调节热效应活性的神经控制中的作用尚不清楚。本研究旨在确定调节MBH神经元活性对交感神经向棕色脂肪组织（BAT）流出、BAT产热和皮肤血管舒缩的影响。通过局部给药muscimol（一种gaba受体激动剂）对MBH神经元进行药理抑制，可减少皮肤冷却诱发的BAT产热、过期二氧化碳、体温、心率和平均动脉压，而在MBH中通过纳米注射双球茎碱阻断gaba受体可诱导BAT交感神经活动（SNA）、BAT温度、体温、过期二氧化碳、心率和皮肤血管收缩的大量增加。MBH的神经元向下丘脑背侧区和下丘脑背内侧区（DMH）的神经元发送投射，刺激中叶白斑吻侧区（rRPa）的交感前运动神经元，控制交感神经向BAT的流出。阻断MBH中gaba受体引起的BAT SNA、BAT温度和过期co2的增加可以通过阻断DMH或rRPa中的兴奋性氨基酸受体来逆转。综上所述，我们的数据表明MBH神经元对BAT产热的冷防御有一定的贡献，而这些神经元的gaba能解除抑制会导致交感神经向BAT的流出大量增加，并导致皮肤血管收缩。BAT上的谷氨酸受体在DMH和rRPa的促热神经元上的激活是MBH神经元去抑制引起的交感神经向BAT流出增加的必要条件。这些数据表明，神经机制有助于控制热效应活性，并可能对调节体温和能量消耗具有重要意义。
The mediobasal hypothalamus (MBH) contains heterogeneous neuronal populations that regulate food intake and energy expenditure. However, the role of MBH neurons in the neural control of thermoeffector activity for thermoregulation is not known. This study sought to determine the effects of modulating the activity of MBH neurons on the sympathetic outflow to brown adipose tissue (BAT), BAT thermogenesis, and cutaneous vasomotion. Pharmacological inhibition of MBH neurons by local administration of muscimol, a GABAAreceptor agonist, reduced skin cooling-evoked BAT thermogenesis, expired CO2, body temperature, heart rate, and mean arterial pressure, while blockade of GABAAreceptors by nanoinjection of bicuculline in the MBH induced large increases in BAT sympathetic nerve activity (SNA), BAT temperature, body temperature, expired CO2, heart rate, and cutaneous vasoconstriction. Neurons in the MBH send projections to neurons in the dorsal hypothalamic area and dorsomedial hypothalamus (DMH), which excite sympathetic premotor neurons in the rostral raphe pallidus area (rRPa) that control sympathetic outflow to BAT. The increases in BAT SNA, BAT temperature, and expired CO2elicited by blockade of GABAAreceptors in the MBH were reversed by blocking excitatory amino acid receptors in the DMH or in the rRPa. Together, our data show that MBH neurons provide a modest contribution to BAT thermogenesis for cold defense, while GABAergic disinhibition of these neurons produces large increases in the sympathetic outflow to BAT, and cutaneous vasoconstriction. Activation of glutamate receptors on BAT thermogenesis-promoting neurons of the DMH and rRPa is necessary for the increased sympathetic outflow to BAT evoked by disinhibition of MBH neurons. These data demonstrate neural mechanisms that contribute to the control of thermoeffector activity, and may have important implications for regulating body temperature and energy expenditure.