Journal
NEURON
Volume 40, Issue 4, Pages 835-845Publisher
CELL PRESS
DOI: 10.1016/S0896-6273(03)00694-9
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Funding
- NIA NIH HHS [AG06036] Funding Source: Medline
- NIMH NIH HHS [MH45481] Funding Source: Medline
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Activation of the cAMP/protein kinase A (PKA) pathway has been proposed as a mechanism for improving age-related cognitive deficits based on studies of hippocampal function. However, normal aging also afflicts prefrontal cortical cognitive functioning. Here, we report that agents that increase PKA activity impair rather than improve prefrontal cortical function in aged rats and monkeys with prefrontal cortical deficits. Conversely, PKA inhibition ameliorates prefrontal cortical cognitive deficits. Western blot and immunohistochemical analyses of rat brain further indicate that the cAMP/PKA pathway becomes disinhibited in the prefrontal cortex with advancing age. These data demonstrate that PKA inhibition, rather than activation, is the appropriate strategy for restoring prefrontal cortical cognitive abilities in the elderly.
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