[HTML][HTML] Dysregulation of protein kinase a signaling in the aged prefrontal cortex: new strategy for treating age-related cognitive decline
BP Ramos, SG Birnbaum, I Lindenmayer, SS Newton… - Neuron, 2003 - cell.com
BP Ramos, SG Birnbaum, I Lindenmayer, SS Newton, RS Duman, AFT Arnsten
Neuron, 2003•cell.comActivation 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 …
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 …
Abstract
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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