The rostral raphe pallidus nucleus mediates pyrogenic transmission from the preoptic area.
Fever is the widely known hallmark of disease and is induced by the action of the nervous system. It is generally accepted that prostaglandin (PG) E(2) is produced in response to immune signals and then acts on the preoptic area (POA), which triggers the stimulation of the sympathetic system, resulting in the production of fever. Actually, the EP3 subtype of PGE receptor, which is essential for the induction of fever, is known to be localized in POA neurons. However, the neural pathway mediating the pyrogenic transmission from the POA to the sympathetic system remains unknown. To identify the neuronal groups involved in the fever-inducing pathway, we first investigated Fos expression in medullary regions of rats after central administrations of PGE(2). PGE(2) application to the lateral ventricle or directly to the POA strikingly increased the number of Fos-positive neurons in the rostral part of the raphe pallidus nucleus (rRPa). Most of these neurons did not exhibit serotonin immunoreactivity. Microinjection of muscimol, a GABA(A) receptor agonist, into the rRPa blocked fever and thermogenesis in brown adipose tissue induced by intra-POA as well as by intracerebroventricular PGE(2) applications. Furthermore, neural tract tracing studies revealed a direct projection from EP3 receptor-expressing POA neurons to the rRPa. Our results demonstrate that the rRPa, which has never been associated with the fever mechanism, mediates the pyrogenic neurotransmission from the POA to the peripheral sympathetic effectors contributing to fever development.
Nakamura
Kazuhiro
K
Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Department of Intelligence Science and Technology, Japan Science and Technology, Sakyo-ku, Kyoto 606-8502, Japan. nkazuhir@pharm.kyoto-u.ac.jp.
Matsumura
Kiyoshi
K
Kaneko
Takeshi
T
Kobayashi
Shigeo
S
Katoh
Hironori
H
Negishi
Manabu
M
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D015232:Dinoprostone / Q000008:administration & dosage; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D005456:Fluorescent Dyes; D018755:GABA Agonists / Q000008:administration & dosage; D058785:GABA-A Receptor Agonists; D005968:Glutamate Decarboxylase / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000008:administration & dosage; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018078:Receptors, Prostaglandin E / Q000096:biosynthesis; D058308:Receptors, Prostaglandin E, EP3 Subtype; D012701:Serotonin / Q000096:biosynthesis; D013266:Stilbamidines; D013564:Sympathetic Nervous System / Q000502:physiology
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D005456:Fluorescent Dyes; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D007527:Isoenzymes; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013266:Stilbamidines; D009118:Muscimol; D012701:Serotonin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D015232:Dinoprostone