Thermoregulatory pathway underlying the pyrogenic effects of prostaglandin E 2 in the lateral parabrachial nucleus of male rats.

Autor: Xu JH; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., He TH; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., Wang NP; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., Gao WM; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., Cheng YJ; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., Ji QF; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., Wu SH; School of Clinical Medicine, Chengdu Medical College, Chengdu, 610500, China., Wei YL; School of Clinical Medicine, Chengdu Medical College, Chengdu, 610500, China., Tang Y; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., Yang WZ; School of Life Science and Technology, Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China. yangwen@shanghaitech.edu.cn., Zhang J; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China. zhangjiefa8888@126.com.
Jazyk: angličtina
Zdroj: Acta pharmacologica Sinica [Acta Pharmacol Sin] 2024 Sep; Vol. 45 (9), pp. 1832-1847. Date of Electronic Publication: 2024 May 03.
DOI: 10.1038/s41401-024-01289-6
Abstrakt: 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 (I A ) 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 thermoeffector reactions to intra-LPBN PGE 2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE 2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of I A currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.
(© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)
Databáze: MEDLINE
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