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

84 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

Funding

Special thanks to W.R. Kinney for his help throughout the course of this study. Supported by a Natural Sciences and Engineering Research Council of Canada Post-doctoral fellowship to R.K.M. and by MH25281-21 to A.R. The authors wish to thank P.J. Meberg for demonstrating the in situ method, I. Cantallops for demonstrating the Timm's stain method, E. Valcourt for technical assistance, and S. Hicks for performing the quantitative densitometry.

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

Fingerprint

Dive into the research topics of 'NMDA receptor blockade prevents kainate induction of protein F1/GAP-43 mRNA in hippocampal granule cells and subsequent mossy fiber sprouting in the rat'. Together they form a unique fingerprint.

Cite this