NMDA receptor blockade prevents kainate induction of protein F1/GAP-43 mRNA in hippocampal granule cells and subsequent mossy fiber sprouting in the rat

Robert K. McNamara, Aryeh Routtenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Granule cells in the adult rat hippocampus do not constitutively express the growth-related axonal protein F1 (a.k.a. B-50, GAP-43, neuromodulin, pp46), yet kainic acid (KA) can induce extensive growth of granule cell axons, the mossy fibers, into the supragranular layer. Does this KA-induced growth occur in the absence of protein Fl/GAP-43? Using quantitative in situ hybridization, we found that 16-24 h after KA (10 mg/kg, s.c.) Fl/GAP-43 mRNA was in fact induced in granule cells and remained elevated above control levels for at least 20 days. The induction of Fl/GAP-43 mRNA in granule cells was blocked either by MK-801 or pentobarbital pretreatment. If pentobarbitol was given 55 min, but not 90 min, after KA, Fl/GAP-43 mRNA was also blocked. Since induction of Fl/GAP-43 occurred when pentobarbitol was given 90 min after KA, a 35 min window of activation is required, beyond the initial 55 min, for F1/GAP-43 mRNA induction. As both MK-801 and pentobarbital blocked behavioral seizures their anti-convulsant action may be important for blocking Fl/GAP-43 mRNA induction. Mossy fiber sprouting observed 30 days after KA was also blocked when either MK-801 or pentobarbital was given prior to KA. These results are consistent with the proposal that protein Fl/GAP-43 promotes axonal growth in the adult brain in an input-dependent manner, and may also be of clinical relevance to the molecular mechanisms underlying structural remodeling in epilepsy.

Original languageEnglish (US)
Pages (from-to)22-28
Number of pages7
JournalMolecular Brain Research
Volume33
Issue number1
DOIs
StatePublished - Oct 1995

Keywords

  • Axonal Growth
  • GAP-43
  • Hippocampus
  • In situ hybridization
  • Kainic acid
  • MK-801
  • Mossy fiber sprouting
  • NMDA receptor
  • Pentobarbital
  • Protein Fl
  • Seizure
  • Timm's stain

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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