Adenoviral vector-directed expression of neurotrophin-3 in rat dorsal root ganglion explants results in a robust neurite outgrowth response

Paul A Dijkhuizen, W.T.J.M.C. Hermens, M A Teunis, J Verhaagen

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

The neurotrophins are a family of proteins that promote neuronal survival and neurite outgrowth during development and can also enhance the regeneration of injured adult neurons. The local and continuous delivery of these proteins at the site of injury is problematic, since this requires repeated intraparenchymal injections or the use of invasive canula-micropump devices. In the present study we report the generation and characterization of an adenoviral vector for a member of the neurotrophins, neurotrophin-3 (Ad-NT-3). Using Ad-NT-3, we examined the expression and biological activity of NT-3 in dorsal root ganglia (DRG) explant cultures. Gene transfer with Ad-NT-3 results in the synthesis of genuine NT-3 and in a dosage-dependent neurite outgrowth response in DRG explants. Transduction of DRG explants with a viral vector dosage of 5 x 10(5) to 5 x 10(6) plaque-forming units induced the formation of a dense halo of neurites comparable to outgrowth observed following the addition of 100 ng/mL exogenous NT-3. In addition, a single infection with Ad-NT-3 produced biologically active NT-3 for at least 20 days in culture, as evidenced by continued neurite extension. This indicates that adenoviral vector-mediated expression of NT-3 results in high-level production of biologically active NT-3 and could therefore be used as a strategy to promote the regeneration of injured peripheral and central nerve projections.

Original languageEnglish
Pages (from-to)172-84
Number of pages13
JournalJournal of Neurobiology
Volume33
Issue number2
Publication statusPublished - Aug 1997

Keywords

  • Adenoviridae
  • Adenoviridae Infections
  • Animals
  • Cells, Cultured
  • DNA, Viral
  • Ganglia, Spinal
  • Gene Expression Regulation, Viral
  • Gene Transfer Techniques
  • Nerve Growth Factors
  • Nerve Regeneration
  • Neurites
  • Neurons
  • Neurotrophin 3
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint Dive into the research topics of 'Adenoviral vector-directed expression of neurotrophin-3 in rat dorsal root ganglion explants results in a robust neurite outgrowth response'. Together they form a unique fingerprint.

  • Cite this