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 language | English |
|---|---|
| Pages (from-to) | 1019-1029 |
| Number of pages | 11 |
| Journal | Journal of Neurochemistry |
| Volume | 123 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 1 2012 |
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Keywords
- cAMP
- fluid-percussion
- inflammation
- isoform
- phosphodiesterase
- traumatic brain injury
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience
Cite this
Phosphodiesterase isoform-specific expression induced by traumatic brain injury. / Oliva, Anthony A.; Kang, Yuan; Furones, Concepcion; Alonso, Ofelia F.; Bruno, Olga; Dalton Dietrich, W.; Atkins, Coleen M.
In: Journal of Neurochemistry, Vol. 123, No. 6, 01.12.2012, p. 1019-1029.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phosphodiesterase isoform-specific expression induced by traumatic brain injury
AU - Oliva, Anthony A.
AU - Kang, Yuan
AU - Furones, Concepcion
AU - Alonso, Ofelia F.
AU - Bruno, Olga
AU - Dalton Dietrich, W.
AU - Atkins, Coleen M
PY - 2012/12/1
Y1 - 2012/12/1
N2 - 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.
AB - 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.
KW - cAMP
KW - fluid-percussion
KW - inflammation
KW - isoform
KW - phosphodiesterase
KW - traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=84870612072&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870612072&partnerID=8YFLogxK
U2 - 10.1111/jnc.12049
DO - 10.1111/jnc.12049
M3 - Article
C2 - 23057870
AN - SCOPUS:84870612072
VL - 123
SP - 1019
EP - 1029
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 6
ER -