Axonal protection by brain-derived neurotrophic factor associated with CREB phosphorylation in tumor necrosis factor-alpha-induced optic nerve degeneration

Acta Neuropathol. 2009 Jan;117(1):75-84. doi: 10.1007/s00401-008-0440-9. Epub 2008 Oct 1.

Abstract

Brain-derived neurotrophic factor (BDNF) is a potent survival and developmental factor that is regulated by cyclic AMP-response element binding protein (CREB) and has a protective effect against retinal ganglion cell (RGC) death. However, the effect of BDNF on the optic nerve axonal degeneration remains to be examined. In this study, we show that intravitreal injection of tumor necrosis factor (TNF)-alpha induces transient increases in phosphorylated-CREB (p-CREB) and BDNF expression in the optic nerve. Administration of exogenous BDNF further increased the p-CREB and endogenous BDNF level and exerted a neuroprotective effect against TNF-alpha-induced axonal loss. The increases in BDNF mRNA and protein induced by TNF-alpha were inhibited significantly by a CRE decoy oligonucleotide. The protective effect of exogenous BDNF on axons was also inhibited by the CRE decoy oligonucleotide. These results suggest that the protective effect of exogenous BDNF may be associated with increases in CREB phosphorylation and endogenous BDNF in the optic nerve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Axons / drug effects*
  • Axons / metabolism
  • Axons / pathology
  • Blotting, Western
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • CREB-Binding Protein / genetics
  • CREB-Binding Protein / metabolism*
  • Immunohistochemistry
  • Male
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology
  • Nerve Degeneration / prevention & control
  • Optic Nerve / drug effects*
  • Optic Nerve / metabolism
  • Optic Nerve / pathology
  • Optic Nerve Diseases / metabolism
  • Optic Nerve Diseases / pathology
  • Optic Nerve Diseases / prevention & control
  • Phosphorylation / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / toxicity*

Substances

  • Brain-Derived Neurotrophic Factor
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • CREB-Binding Protein