title: Sex differences in brain proteomes of neuron-specific STAT3-null mice after cerebral ischemia/reperfusion.
abstract: Signal transduction and activator of transcription-3 (STAT3) plays an important role in neuronal survival, regeneration and repair after brain injury. We previously demonstrated that STAT3 is activated in brain after cerebral ischemia specifically in neurons. The effect was sex-specific and modulated by sex steroids, with higher activation in females than males. In the current study, we used a proteomics approach to identify downstream proteins affected by ischemia in male and female wild-type (WT) and neuron-specific STAT3 knockout (KO) mice. We established four comparison groups based on the transgenic condition and the hemisphere analyzed, respectively. Moreover, the sexual variable was taken into account and male and female animals were analyzed independently. Results support a role for STAT3 in metabolic, synaptic, structural and transcriptional responses to cerebral ischemia, indeed the adaptive response to ischemia/reperfusion injury is delayed in neuronal-specific STAT3 KO mice. The differences observed between males and females emphasize the importance of sex-specific neuronal survival and repair mechanisms, especially those involving antioxidant and energy-related activities, often caused by sex hormones.
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Domenico
authors.forename: Gabriella
authors.initials: G
authors.lastname: Casalena
authors.forename: Jia
authors.initials: J
authors.lastname: Jia
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.forename: Eugenio
authors.initials: E
authors.lastname: Barone
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.forename: William M
authors.initials: WM
authors.lastname: Pierce
authors.forename: Chiara
authors.initials: C
authors.lastname: Cini
authors.forename: Cesare
authors.initials: C
authors.lastname: Mancuso
authors.forename: Marzia
authors.initials: M
authors.lastname: Perluigi
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Davis
authors.forename: Nabil J
authors.initials: NJ
authors.lastname: Alkayed
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
authors.forename: Allan D
authors.initials: AD
authors.lastname: Butterfield
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000502:physiology*; D001923:Brain Chemistry / Q000235:genetics*; D002545:Brain Ischemia / Q000235:genetics* / Q000503:physiopathology; D002874:Chromosome Mapping; D004396:Coloring Agents; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020543:Proteome; D015427:Reperfusion Injury / Q000235:genetics* / Q000503:physiopathology; D015203:Reproducibility of Results; D050796:STAT3 Transcription Factor / Q000235:genetics*; D012727:Sex Characteristics; D014357:Trypsin / Q000737:chemistry
chemical_list: D004396:Coloring Agents; D020543:Proteome; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014357:Trypsin