Age-dependent alterations in cAMP signaling contribute to synaptic plasticity deficits following traumatic brain injury

D. J. Titus, C. Furones, Y. Kang, Coleen M Atkins

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 languageEnglish
Pages (from-to)182-194
Number of pages13
JournalNeuroscience
Volume231
DOIs
StatePublished - Feb 2 2013

Fingerprint

Neuronal Plasticity
Brain Concussion
Long-Term Potentiation
Young Adult
Hippocampus
Rolipram
Adenylate Kinase
Parietal Lobe
Cyclic AMP-Dependent Protein Kinases
Thalamus
Cyclic AMP
Percussion
Traumatic Brain Injury
Long-Term Memory
Inbred F344 Rats
Atmosphere
Brain Injuries
Theoretical Models
Down-Regulation
Age Groups

Keywords

  • CAMP
  • Fluid-percussion
  • Long-term potentiation
  • Phosphodiesterase
  • Rolipram
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Age-dependent alterations in cAMP signaling contribute to synaptic plasticity deficits following traumatic brain injury. / Titus, D. J.; Furones, C.; Kang, Y.; Atkins, Coleen M.

In: Neuroscience, Vol. 231, 02.02.2013, p. 182-194.

Research output: Contribution to journalArticle

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