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Serotonin stimulates mitochondrial transport in hippocampal neurons

Academic Article
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Overview

authors

  • Chen, S.
  • Owens, G. C.
  • Crossin, Kathryn
  • Edelman, D. B.

publication date

  • December 2007

journal

  • Molecular and Cellular Neuroscience  Journal

abstract

  • Axonal transport of mitochondria is critical for proper neuronal function. However, little is known about the extracellular signals that regulate this process. In the present study, we show that the neuromodulator serotonin (5-HT) greatly enhances mitochondrial movement in the axons of rat hippocampal neurons in vitro. Administration of a 5-HT1A receptor antagonist inhibited mitochondrial movement, whereas addition of fluoxetine, a selective serotonin reuptake inhibitor, promoted mitochondrial movement. 5-HT receptors are known to activate the Akt/Protein kinase B pathway. Consistent with this, directional mitochondrial movement was almost completely blocked by a specific Akt inhibitor. Moreover, an inhibitor of glycogen synthase kinase-3beta (GSK3beta), a kinase whose activity is blocked by Akt-mediated phosphorylation, promoted mitochondrial movement. These findings show that 5-HT1A receptor activation stimulates mitochondrial movement in hippocampal neurons by inhibiting GSK3beta activity via Akt. Our findings suggest that 5-HT may mediate the redistribution of energy sources within responsive neurons, a possibility that has significant implications for understanding the global biological effects of this important neuromodulator.

subject areas

  • Animals
  • Axonal Transport
  • Axons
  • Cell Line
  • Cells, Cultured
  • Energy Metabolism
  • Enzyme Inhibitors
  • Glycogen Synthase Kinase 3
  • Hippocampus
  • Humans
  • Mitochondria
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Signal Transduction
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Research

keywords

  • 5-HT
  • Akt
  • GSK3 beta
  • axonal transport
  • mitochondria
  • serotonin
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Identity

International Standard Serial Number (ISSN)

  • 1044-7431

Digital Object Identifier (DOI)

  • 10.1016/j.mcn.2007.08.004

PubMed ID

  • 17904380
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Additional Document Info

start page

  • 472

end page

  • 483

volume

  • 36

issue

  • 4

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