Serotonin and neuronal growth factors - a convergence of signaling pathways.
Monoamines, including serotonin (5-HT), have traditionally been associated with short-term signaling pathways in neurons, such as the modulation of cAMP and Ca(2+) levels. In contrast, neuronal growth factors, such as neurotrophins, have been traditionally associated with signaling pathways, such as those for activation of extracellular-regulated kinase (ERK) and Akt (protein kinase B), which are known to induce long-term protective changes. It has therefore been unclear how antidepressants that increase serotonin (5-HT), induce such changes as hippocampal neuroprotection and neurogenesis. It has been hypothesized, that the actions of 5-HT may be mediated indirectly through increased synthesis of peptide growth factors. However, there is increasing evidence that some subtypes of 5-HT receptors can directly couple to activation of the ERK and Akt pathways. Such coupling suggests a more direct potential role for 5-HT in mediating the long-term actions induced by antidepressants.
Cowen
Daniel S
DS
Department of Psychiatry, University of Medicine and Dentistry of New Jersey - Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, USA. cowends@umdnj.edu
D000818:Animals; D009414:Nerve Growth Factors / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D009414:Nerve Growth Factors; D012701:Serotonin