title: Involvement of Stat3 in mouse brain development and sexual dimorphism: a proteomics approach.
abstract: Although the role of STAT3 in cell physiology and tissue development has been largely investigated, its involvement in the development and maintenance of nervous tissue and in the mechanisms of neuroprotection is not yet known. The potentially wide range of STAT3 activities raises the question of tissue- and gender-specificity as putative mechanisms of regulation. To explore the function of STAT3 in the brain and the hypothesis of a gender-linked modulation of STAT3, we analyzed a neuron-specific STAT3 knockout mouse model investigating the influence of STAT3 activity in brain protein expression pattern in both males and females in the absence of neurological insult. We performed a proteomic study aimed to reveal the molecular pathways directly or indirectly controlled by STAT3 underscoring its role in brain development and maintenance. We identified several proteins, belonging to different neuronal pathways such as energy metabolism or synaptic transmission, controlled by STAT3 that confirm its crucial role in brain development and maintenance. Moreover, we investigated the different processes that could contribute to the sexual dimorphic behavior observed in the incidence of neurological and mental disease. Interestingly both STAT3 KO and gender factors influence the expression of several mitochondrial proteins conferring to mitochondrial activity high importance in the regulation of brain physiology and conceivable relevance as therapeutic target.
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Domenico
authors.forename: Gabriella
authors.initials: G
authors.lastname: Casalena
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.forename: William M
authors.initials: WM
authors.lastname: Pierce
authors.forename: Marzia
authors.initials: M
authors.lastname: Perluigi
authors.forename: Chiara
authors.initials: C
authors.lastname: Cini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Baracca
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Solaini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lenaz
authors.forename: Jia
authors.initials: J
authors.lastname: Jia
authors.forename: Suzan
authors.initials: S
authors.lastname: Dziennis
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Murphy
authors.forename: Nabil J
authors.initials: NJ
authors.lastname: Alkayed
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D040901:Proteomics / Q000379:methods*; D050796:STAT3 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012727:Sex Characteristics
chemical_list: D009419:Nerve Tissue Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse