Phosphodiesterase isoform-specific expression induced by traumatic brain injury

Anthony A. Oliva, Yuan Kang, Concepcion Furones, Ofelia F. Alonso, Olga Bruno, W. Dalton Dietrich, Coleen M. Atkins

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Traumatic brain injury (TBI) results in significant inflammation which contributes to the evolving pathology. Previously, we have demonstrated that cyclic AMP (cAMP), a molecule involved in inflammation, is down-regulated after TBI. To determine the mechanism by which cAMP is down-regulated after TBI, we determined whether TBI induces changes in phosphodiesterase (PDE) expression. Adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury (FPI) or sham injury, and the ipsilateral, parietal cortex was analyzed by western blotting. In the ipsilateral parietal cortex, expression of PDE1A, PDE4B2, and PDE4D2, significantly increased from 30 min to 24 h post-injury. PDE10A significantly increased at 6 and 24 h after TBI. Phosphorylation of PDE4A significantly increased from 6 h to 7 days post-injury. In contrast, PDE1B, PD4A5, and PDE4A8 significantly decreased after TBI. No changes were observed with PDE1C, PDE3A, PDE4B1/3, PDE4B4, PDE4D3, PDE4D4, PDE8A, or PDE8B. Co-localization studies showed that PDE1A, PDE4B2, and phospho-PDE4A were neuronally expressed, whereas PDE4D2 was expressed in neither neurons nor glia. These findings suggest that therapies to reduce inflammation after TBI could be facilitated with targeted therapies, in particular for PDE1A, PDE4B2, PDE4D2, or PDE10A. Injury-Specific Changes in Phosphodiesterases after Traumatic Brain Injury To identify injury-specific therapeutic targets for the treatment of traumatic brain injury (TBI), we investigated changes in phosphodiesterases (PDEs) after TBI. We found that PDE1A, 4B2, 4D2, and 10A significantly increased after TBI. These results indicate that targeting these particular PDE isoforms may be more therapeutically relevant than broad-spectrum PDE inhibitors.

Original languageEnglish (US)
Pages (from-to)1019-1029
Number of pages11
JournalJournal of neurochemistry
Volume123
Issue number6
DOIs
StatePublished - Dec 1 2012

Keywords

  • cAMP
  • fluid-percussion
  • inflammation
  • isoform
  • phosphodiesterase
  • traumatic brain injury

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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