Activity-dependent neurotrophic factor-9 and NAP promote neurite outgrowth in rat hippocampal and cortical cultures.
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.
Smith-Swintosky
Virginia L
VL
CNS Research, Johnson & Johnson Pharmaceutical Research and Development, LLC, Spring House, PA 19447-0776, USA. vswintos@prdus.jnj.com
Gozes
Illana
I
Brenneman
Douglas E
DE
D'Andrea
Michael R
MR
Plata-Salaman
Carlos R
CR
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005260:Female; D006624:Hippocampus / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D009842:Oligopeptides / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D016708:Synaptophysin / Q000378:metabolism
D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D016708:Synaptophysin; C425904:davunetide