TY - JOUR
T1 - Dysregulation of protein kinase A signaling in the aged prefrontal cortex
T2 - New strategy for treating age-related cognitive decline
AU - Ramos, Brian P.
AU - Birnbaum, Shari G.
AU - Lindenmayer, Isabelle
AU - Newton, Samuel S.
AU - Duman, Ronald S.
AU - Arnsten, Amy F.T.
PY - 2003/11/13
Y1 - 2003/11/13
N2 - 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.
AB - 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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U2 - 10.1016/S0896-6273(03)00694-9
DO - 10.1016/S0896-6273(03)00694-9
M3 - Article
C2 - 14622586
AN - SCOPUS:0242460552
VL - 40
SP - 835
EP - 845
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 4
ER -