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DNC Alterations Underlying Age-related Cognitive Decline

Reduced PFC Network Firing with Advancing Age

Prefrontal cortical functions weaken with advancing age in both animals and humans. There is an increase in Ca2+-cAMP signaling in PFC that correlates with cognitive deficits, and a selective loss of long, thin spines from the monkey dlPFC. Physiological recordings have shown that the persistent firing needed for working memory markedly declines with age, and is restored by inhibiting Ca2+-cAMP signaling, e.g. with guanfacine. Understanding these mechanisms may allow us to treat age-related cognitive deficits that afflict the association cortices.

If you are interested:

  • Wang et al. (2011) Neuronal basis of age-related working memory decline. Nature 476: 210-3.
  • Morrison and Baxter (2012) The ageing cortical synapse: hallmarks and implications for cognitive decline. Nat Rev Neurosci. 13: 240-50.
  • Brennan et al. (2009) Protein kinase C activity is associated with prefrontal cortical decline in aging. Neurobiol Aging 30:782-92.
  • Ramos et al. (2003) Dysregulation of protein kinase a signaling in the aged prefrontal cortex: new strategy for treating age-related cognitive decline. Neuron 40: 835-45.