Activity-dependent neurotrophic factor-9 and NAP promote neurite outgrowth in rat hippocampal and cortical cultures

J Mol Neurosci. 2005;25(3):225-38. doi: 10.1385/JMN:25:3:225.


Activity-dependent neurotrophic factor (ADNF) is a novel, femtomolar-acting, glial-derived polypeptide (14 kDa) known to protect neurons from a variety of toxic insults. The active site for ADNF function is localized to a 9-amino-acid stretch (SALLRSIPA; ADNF-9). A few years later, a novel ADNF-9-like active peptide (NAPVSIPQ or NAP) was identified and shown to be expressed in the CNS and exhibit an activity profile similar to ADNF-9. Such studies suggest that ADNF-9 and NAP might function like other known neurotrophins and play a role in neural development and maintenance. The purpose of the present studies was to determine if ADNF-9 or NAP affects neurite outgrowth and synaptogenesis in rat hippocampal and cortical cultures. Using MAP2-FITC immunofluorescent labeling, we found that ADNF-9 and NAP promoted neurite outgrowth in a concentration-dependent manner, with maximal activity observed at femtomolar concentrations. Both peptides stimulated robust outgrowth in hippocampal cells (approximately 150% of control; p < 0.01) with a modest effect on cortical cells (approximately 20% of control; p < 0.05) similar to other known growth factors. However, the outgrowth-promoting effect was abolished in the absence of serum, suggesting that soluble factors might be necessary for the neurotrophic activity. Finally, we found that ADNF-9 and NAP increased synaptophysin expression in both rat hippocampal and cortical cultures. These results suggest that ADNF-9 and NAP might contribute to neuronal plasticity associated with development and repair after injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Female
  • Hippocampus / cytology
  • Nerve Tissue Proteins / pharmacology*
  • Neurites / drug effects*
  • Neurites / physiology*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Oligopeptides / pharmacology*
  • Pregnancy
  • Rats
  • Synaptophysin / metabolism


  • Nerve Tissue Proteins
  • Oligopeptides
  • Synaptophysin
  • davunetide