NGF promotes long-term memory formation by activating poly(ADP-ribose)polymerase-1

Neuropharmacology. 2012 Nov;63(6):1085-92. doi: 10.1016/j.neuropharm.2012.06.050. Epub 2012 Jul 4.


Nerve growth factor (NGF) is a critical secreted protein that plays an important role in development, survival, and function of the mammalian nervous system. Previously reports suggest that endogenous NGF is essential for the hippocampal plasticity/memory and NGF deprivation induces the impairment of hippocampus-related memory and synaptic plasticity. However, whether exogenous supplement of NGF could promote the hippocampus-dependent synaptic plasticity/memory and the possible underlying mechanisms are not clear. In this study we found that NGF administration facilitates the hippocampus-dependent long-term memory and synaptic plasticity by increasing the activity of PARP-1, a polymerase mediating the PolyADP-ribosylation and important for the memory formation. Co-application of 3-Aminobenzamide (3-AB), a specific inhibitor of PARP-1, distinctly blocked the boosting effect of NGF on memory and synaptic plasticity, and the activation of downstream PKA-CREB signal pathway. Our data provide the first evidence that NGF supplement facilitates synaptic plasticity and the memory ability through PARP-1-mediated protein polyADP-ribosylation and activation of PKA-CREB pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Benzamides / pharmacology
  • Blotting, Western
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Electrophysiological Phenomena
  • Enzyme Activation / drug effects
  • Fear / psychology
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Immunohistochemistry
  • Long-Term Potentiation / drug effects
  • Male
  • Maze Learning / drug effects
  • Memory, Long-Term / drug effects*
  • Nerve Growth Factor / pharmacology*
  • Neuronal Plasticity / drug effects
  • Phosphorylation
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / drug effects
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Rats
  • Rats, Wistar
  • Synaptosomes / drug effects


  • Benzamides
  • Cyclic AMP Response Element-Binding Protein
  • 3-aminobenzamide
  • Nerve Growth Factor
  • Parp1 protein, rat
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Cyclic AMP-Dependent Protein Kinases