Immunohistochemical evidence of functional leptin receptor expression in neuronal and endothelial cells of the rat brain.
Leptin binding to its functional receptor leads to activation of the JAK-STAT-signaling pathway and especially to the activation of the signal transducer and activator of transcription factor 3 (STAT3). The immunohistochemical detection of nuclear STAT3 translocation is used as a neuroanatomical mapping tool to determine leptin-responsive cells in the rat brain. This study neuroanatomically identifies those brain cell phenotypes showing STAT3 activation after intraperitoneal leptin treatment (5 mg/kg) using immunohistochemical colocalization with neuronal and endothelial cell marker proteins. Leptin treatment induced nuclear STAT3 signals with the strongest response observed 90min after the treatment. The caudobasal hypothalamus showed a particularly pronounced STAT3 response. Leptin-induced nuclear STAT3 signals were additionally determined in the solitary tract nucleus, the choroid plexus and in the brain endothelium. The vast majority of STAT3-responsive cells proved to be neurons located in the caudobasal hypothalamus, however, a marked number of brain endothelial cells distributed throughout the entire brain got activated as well. In conclusion, neurons and non-neuronal brain cells, e.g., endothelial or choroid plexus cells, seem to express functional leptin receptors and might thereby mediate leptin-dependent functions in the rat brain.
Mütze
Jörg
J
Veterinary-Physiology, Justus-Liebig-University Giessen, Germany.
Roth
Joachim
J
Gerstberger
Rüdiger
R
Matsumura
Kiyoshi
K
Hübschle
Thomas
T
D000818:Animals; D000941:Antigens / Q000378:metabolism; D001921:Brain / Q000166:cytology*; D042783:Endothelial Cells / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D020738:Leptin / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013997:Time Factors; D014841:von Willebrand Factor / Q000276:immunology
D000941:Antigens; D007211:Indoles; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; C007293:DAPI; D010751:Phosphopyruvate Hydratase