Effects of fluvoxamine on nerve growth factor-induced neurite outgrowth inhibition by dexamethasone in PC12 cells

Biosci Biotechnol Biochem. 2019 Apr;83(4):659-665. doi: 10.1080/09168451.2018.1553607. Epub 2018 Dec 13.

Abstract

In the present study, we examined the effects of fluvoxamine on nerve growth factor (NGF)-induced neurite outgrowth inhibition by dexamethasone (DEX) in PC12 cells. Fluvoxamine increased NGF-induced neurite outgrowth. Compared with co-treatment with NGF and fluvoxamine, p-Akt levels were higher than the values without fluvoxamine. The phosphorylated extracellular regulated kinase 1/2 levels were slightly increased by co-treatment with NGF and fluvoxamine. Fluvoxamine concentration-dependently improved NGF-induced neurite outgrowth inhibition by DEX. Fluvoxamine also improved the decrease in the NGF-induced p-Akt level caused by DEX. Interestingly, the sigma-1 receptor antagonist NE-100 blocked the improvement effects of fluvoxamine on NGF-induced neurite outgrowth inhibition by DEX. The selective sigma-1 receptor agonist PRE-084 also improved NGF-induced neurite outgrowth inhibition by DEX, which is blocked by NE-100. These results indicate that the improvement effects of fluvoxamine on NGF-induced neurite outgrowth inhibition by DEX may be attributable to the phosphorylation of Akt and the sigma-1 receptor.

Keywords: Nerve growth factor (NGF); dexamethasone (DEX); fluvoxamine; neurite outgrowth; phosphorylated Akt.

MeSH terms

  • Animals
  • Anisoles / pharmacology
  • Anti-Anxiety Agents / pharmacology*
  • Cell Differentiation / drug effects
  • Dexamethasone / antagonists & inhibitors
  • Dexamethasone / pharmacology
  • Fluvoxamine / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Glucocorticoids / antagonists & inhibitors
  • Glucocorticoids / pharmacology
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Morpholines / pharmacology
  • Nerve Growth Factor / pharmacology
  • Neuronal Outgrowth / drug effects*
  • Neuronal Outgrowth / genetics
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • PC12 Cells
  • Phosphorylation / drug effects
  • Propylamines / pharmacology
  • Proto-Oncogene Proteins c-akt / agonists
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Receptors, sigma / agonists
  • Receptors, sigma / antagonists & inhibitors
  • Receptors, sigma / genetics
  • Receptors, sigma / metabolism
  • Sigma-1 Receptor
  • Signal Transduction

Substances

  • Anisoles
  • Anti-Anxiety Agents
  • Glucocorticoids
  • Morpholines
  • Propylamines
  • Receptors, sigma
  • 2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate
  • N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride
  • Dexamethasone
  • Nerve Growth Factor
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Fluvoxamine