title: Neuroprotection by leptin in a rat model of permanent cerebral ischemia: effects on STAT3 phosphorylation in discrete cells of the brain.
abstract: In addition to its effects in the hypothalamus to control body weight, leptin is involved in the regulation of neuronal function, development and survival. Recent findings have highlighted the neuroprotective effects of leptin against ischemic brain injury; however, to date, little is known about the role performed by the signal transducer and activator of transcription (STAT)-3, a major mediator of leptin receptor transduction pathway in the brain, in the beneficial effects of the hormone. Our data demonstrate that systemic acute administration of leptin produces neuroprotection in rats subjected to permanent middle cerebral artery occlusion (MCAo), as revealed by a significant reduction of the brain infarct volume and neurological deficit up to 7 days after the induction of ischemia. By combining a subcellular fractionation approach with immunohistofluorescence, we observe that neuroprotection is associated with a cell type-specific modulation of STAT3 phosphorylation in the ischemic cortex. The early enhancement of nuclear phospho-STAT3 induced by leptin in the astrocytes of the ischemic penumbra may contribute to a beneficial effect of these cells on the evolution of tissue damage. In addition, the elevation of phospho-STAT3 induced by leptin in the neurons after 24 h MCAo is associated with an increased expression of tissue inhibitor of matrix metalloproteinases-1 in the cortex, suggesting its possible involvement to the neuroprotection produced by the adipokine.
authors.affiliation: Department of Pharmacobiology and University Consortium for the Study of Adaptive Disorders and Head Pain, Section of Neuropharmacology of Normal and Pathological Neuronal Plasticity, University of Calabria, Rende (CS), Italy. amantea@unical.it
authors.forename: D
authors.initials: D
authors.lastname: Amantea
authors.forename: C
authors.initials: C
authors.lastname: Tassorelli
authors.forename: R
authors.initials: R
authors.lastname: Russo
authors.forename: F
authors.initials: F
authors.lastname: Petrelli
authors.forename: L A
authors.initials: LA
authors.lastname: Morrone
authors.forename: G
authors.initials: G
authors.lastname: Bagetta
authors.forename: M T
authors.initials: MT
authors.lastname: Corasaniti
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D054392:Adipokines; D020738:Leptin; D050796:STAT3 Transcription Factor; D019715:Tissue Inhibitor of Metalloproteinase-1