TY - JOUR
T1 - Sex differences in brain proteomes of neuron-specific STAT3-null mice after cerebral ischemia/reperfusion
AU - Di Domenico, Fabio
AU - Casalena, Gabriella
AU - Jia, Jia
AU - Sultana, Rukhsana
AU - Barone, Eugenio
AU - Cai, Jian
AU - Pierce, William M.
AU - Cini, Chiara
AU - Mancuso, Cesare
AU - Perluigi, Marzia
AU - Davis, Catherine M.
AU - Alkayed, Nabil J.
AU - Butterfield, Allan D.
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
KW - Middle cerebral artery occlusion
KW - Proteomics
KW - Sexual dimorphism
KW - Signal transduction and activator of transcription-3
KW - Stroke
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U2 - 10.1111/j.1471-4159.2012.07721.x
DO - 10.1111/j.1471-4159.2012.07721.x
M3 - Article
C2 - 22394374
AN - SCOPUS:84859747516
SN - 0022-3042
VL - 121
SP - 680
EP - 692
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 4
ER -