Thermoregulatory pathway underlying the pyrogenic effects of prostaglandin E_(2) in the lateral parabrachial nucleus of male rats  

作　　者：Jian-hui Xu Tian-hui He Nan-ping Wang Wen-min Gao Yong-jing Cheng Qiao-feng Ji Si-hao Wu Yan-lin Wei Yu Tang Wen Z.Yang Jie Zhang 

机构地区：[1]Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes,Chengdu Medical College,Chengdu,610500,China [2]School of Clinical Medicine,Chengdu Medical College,Chengdu,610500,China [3]School of Life Science and Technology,Shanghai Institute for Advanced Immunochemical Studies,ShanghaiTech University,Shanghai,201210,China

出　　处：《Acta Pharmacologica Sinica》2024年第9期1832-1847,共16页中国药理学报（英文版）

基　　金：National Natural Science Foundation of China(32100926(JHX)and 31771289(JZ));Disciplinary Contraction Innovation Team Foundation(CMC-XK-21XX);Graduates Innovating Experimentation Project(YCX2022-01,THH)of Chengdu Medical College.

摘　　要：It has been shown that prostaglandin(PG)E_(2) synthesized in the lateral parabrachial nucleus(LPBN)is involved in lipopolysaccharide-induced fever.But the neural mechanisms of how intra-LPBN PGE_(2) induces fever remain unclear.In this study,we investigated whether the LPBN-preoptic area(POA)pathway,the thermoafferent pathway for feed-forward thermoregulatory responses,mediates fever induced by intra-LPBN PGE_(2) in male rats.The core temperature(T_(core))was monitored using a temperature radiotelemetry transponder implanted in rat abdomen.We showed that microinjection of PGE_(2)(0.28 nmol)into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area(MnPO).The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE_(2).We demonstrated that EP3 receptor was a pivotal receptor for PGE_(2)-induced fever,since microinjection of EP3 receptor agonist sulprostone(0.2 nmol)or EP3 receptor antagonist L-798106(2 nmol)into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE_(2),respectively,but this was not the case for EP4 and EP1 receptors.Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral(el)and dorsal(d)LPBN were excited and inhibited,respectively,by PGE_(2) perfusion,initiating heat-gain and heat-loss mechanisms.The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents(sEPSCs and mEPSCs)in MnPO-projecting LPBel neurons increased after perfusion with PGE_(2);whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents(sIPSCs)and the A-type potassium(IA)current density did not change.In MnPO-projecting LPBd neurons,neither sEPSCs nor sIPSCs responded to PGE_(2);however,the I_(A) current density was significantly increased by PGE_(2) perfusion.These electrophysiological responses and the

关 键 词：lateral parabrachial nucleus preoptic area FEVER PGE_(2) EP3 receptor A-type potassium current 

分 类 号：R96[医药卫生—药理学]