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 language | English (US) |
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Pages (from-to) | 22-28 |
Number of pages | 7 |
Journal | Molecular Brain Research |
Volume | 33 |
Issue number | 1 |
DOIs | |
State | Published - 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