Abstract
The elderly have comparatively worse cognitive impairments from traumatic brain injury (TBI) relative to younger adults, but the molecular mechanisms that underlie this exacerbation of cognitive deficits are unknown. Experimental models of TBI have demonstrated that the cyclic AMP-protein kinase A (cAMP-PKA) signaling pathway is downregulated after brain trauma. Since the cAMP-PKA signaling pathway is a key mediator of long-term memory formation, we investigated whether the TBI-induced decrease in cAMP levels is exacerbated in aged animals. Aged (19. months) and young adult (3. months) male Fischer 344 rats received sham surgery or mild (1.4-1.6 atmospheres, atm) or moderate (1.7-2.1. atm) parasagittal fluid-percussion brain injury. At various time points after surgery, the ipsilateral parietal cortex, hippocampus, and thalamus were assayed for cAMP levels. Mild TBI lowered cAMP levels in the hippocampus of aged, but not young adult animals. Moderate TBI lowered cAMP levels in the hippocampus and parietal cortex of both age groups. In the thalamus, cAMP levels were significantly lowered after moderate, but not mild TBI. To determine if the TBI-induced decreases in cAMP had physiological consequences in aged animals, hippocampal long-term potentiation (LTP) in the Schaffer collateral pathway of the CA1 region was assessed. LTP was significantly decreased in both young adult and aged animals after mild and moderate TBI as compared to sham surgery animals. Rolipram rescued the LTP deficits after mild TBI for young adult animals and caused a partial recovery for aged animals. However, rolipram did not rescue LTP deficits after moderate TBI in either young adult or aged animals. These results indicate that the exacerbation of cognitive impairments in aged animals with TBI may be due to decreased cAMP levels and deficits in hippocampal LTP.
Original language | English (US) |
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Pages (from-to) | 182-194 |
Number of pages | 13 |
Journal | Neuroscience |
Volume | 231 |
DOIs | |
State | Published - Feb 2 2013 |
Externally published | Yes |
Bibliographical note
Funding Information:The authors thank Dayaris Morffi for technical assistance and Drs. W. Dalton Dietrich, H.M. Bramlett, I. Hentall, and Kaming Lo for critical reading of the manuscript. We thank the University of Miami Biostatistics Collaboration and Consulting Core for statistical support. This work was supported by NIH Grants AG033266 , NS069721 , NS056072 and The Miami Project to Cure Paralysis.
Keywords
- CAMP
- Fluid-percussion
- Long-term potentiation
- Phosphodiesterase
- Rolipram
- Traumatic brain injury