Involvement of Stat3 in mouse brain development and sexual dimorphism: a proteomics approach.
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.
Di Domenico
Fabio
F
Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA.
Casalena
Gabriella
G
Sultana
Rukhsana
R
Cai
Jian
J
Pierce
William M
WM
Perluigi
Marzia
M
Cini
Chiara
C
Baracca
Alessandra
A
Solaini
Giancarlo
G
Lenaz
Giorgio
G
Jia
Jia
J
Dziennis
Suzan
S
Murphy
Stephanie J
SJ
Alkayed
Nabil J
NJ
Butterfield
D Allan
DA
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
D009419:Nerve Tissue Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse