Sex differences in brain proteomes of neuron-specific STAT3-null mice after cerebral ischemia/reperfusion

Fabio Di Domenico, Gabriella Casalena, Jia Jia, Rukhsana Sultana, Eugenio Barone, Jian Cai, William M. Pierce, Chiara Cini, Cesare Mancuso, Marzia Perluigi, Catherine M. Davis, Nabil J. Alkayed, Allan D. Butterfield

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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.

Original languageEnglish
Pages (from-to)680-692
Number of pages13
JournalJournal of Neurochemistry
Issue number4
StatePublished - May 2012


  • Middle cerebral artery occlusion
  • Proteomics
  • Sexual dimorphism
  • Signal transduction and activator of transcription-3
  • Stroke

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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