Detection of structural and metabolic changes in traumatically injured hippocampus by quantitative differential proteomics

Ping Wu, Yingxin Zhao, Sigmund J. Haidacher, Enyin Wang, Margaret O. Parsley, Junling Gao, Rovshan G. Sadygov, Jonathan Starkey, Bruce Luxon, Heidi Spratt, Douglas S. Dewitt, Donald S. Prough, Larry Denner

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Traumatic brain injury (TBI) is a complex and common problem resulting in the loss of cognitive function. In order to build a comprehensive knowledge base of the proteins that underlie these cognitive deficits, we employed unbiased quantitative mass spectrometry, proteomics, and bioinformatics to identify and quantify dysregulated proteins in the CA3 subregion of the hippocampus in the fluid percussion model of TBI in rats. Using stable isotope 18O-water differential labeling and multidimensional tandem liquid chromatography (LC)-MS/MS with high stringency statistical analyses and filtering, we identified and quantified 1002 common proteins, with 124 increased and 76 decreased. The Ingenuity Pathway Analysis (IPA) bioinformatics tool identified that TBI had profound effects on downregulating global energy metabolism, including glycolysis, the Krebs cycle, and oxidative phosphorylation, as well as cellular structure and function. Widespread upregulation of actin-related cytoskeletal dynamics was also found. IPA indicated a common integrative signaling node, calcineurin B1 (CANB1, CaNBα, or PPP3R1), which was downregulated by TBI. Western blotting confirmed that the calcineurin regulatory subunit, CANB1, and its catalytic binding partner PP2BA, were decreased without changes in other calcineurin subunits. CANB1 plays a critical role in downregulated networks of calcium signaling and homeostasis through calmodulin and calmodulin-dependent kinase II to highly interconnected structural networks dominated by tubulins. This large-scale knowledge base lays the foundation for the identification of novel therapeutic targets for cognitive rescue in TBI.

Original languageEnglish (US)
Pages (from-to)775-788
Number of pages14
JournalJournal of neurotrauma
Issue number9
StatePublished - May 1 2013


  • Animal models
  • Bioinformatics
  • Mass spectrometry
  • Proteomics
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology


Dive into the research topics of 'Detection of structural and metabolic changes in traumatically injured hippocampus by quantitative differential proteomics'. Together they form a unique fingerprint.

Cite this