Skip to main content
. Author manuscript; available in PMC: 2014 Jul 7.
Published in final edited form as: Nat Rev Neurosci. 2012 Jan 18;13(3):209–216. doi: 10.1038/nrn3151

Figure 3. Potential for mechanistic synergy between exercise and pharmacological treatments designed to maintain cognition in an aging population.

Figure 3

The locus coeruleus (LC) projection to the hippocampus is essential for exercise-induced brain-derived neurotrophic factor (BDNF) expression. Exercise enhances hippocampal BDNF synthesis, leading to activation of the extracellular signal-related kinase (ERK) pathway, which converges on the transcription factor cyclic adenosine monophosphate (cAMP) response element binding protein (CREB). Treatment with drugs that block norepinephrine (NE) reuptake enhance noradrenergic neurotransmission, leading to activation of adenyl cyclase and cAMP, which also activates CREB, leading to transcription of a number of different genes associated with synaptic plasticity and neurogenesis. Concurrent exercise and norepinephrine reuptake inhibitor treatment could additively enhance hippocampal BDNF production and be neuroprotective. AMPA, {alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA, N-methyl-D-aspartate; TrkB, high-affinity BDNF receptor; CamKII, calcium calmodulin kinase II; MEK1/2, mitogen-activated protein kinase kinase 2; ERK, extracellular-signal related kinase; P, phosphorylation site.