Relationship between GAP-43 expression in the dentate gyrus and synaptic reorganization of hippocampal messy fibres in rats treated with kainic acid

C. Bendotti, S. Baldessari, M. Pende, T. Southgate, F. Guglimetti, R. Samanin

Research output: Contribution to journalArticle

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Abstract

Kainic acid-induced seizures in adult rats produce neurodegeneration in the hippocampus followed by sprouting of the messy fibres in the inner molecular layer of the dentate gyrus and changes in GAP-43 expression in the granule cells. In the present study we observed that 4 days after kainic acid injection a dense plexus of silver-impregnated degenerating terminals detected by Gallyas's method and a decrease of GAP-43 immunostaining was observed in the inner molecular layer of the dentate gyrus indicating deafferentiation of this region. This was associated with the formation of an intense GAP-43 immunostained band in the supragranular layer. MK-801, a non-competitive inhibitor of the NMDA receptor, which partially inhibited the behavioural seizures induced by KA, also protected from the inner molecular layer deafferentation and markedly reduced the expression of GAP-43 mRNA in the granule cells and the intense GAP-43 immunostained band in the supragranular layer, suggesting a relationship among these events. Two months after kainic acid injection the intense supragranular GAP-43 positive band was no longer evident but the whole inner molecular layer appeared more labelled in association with the formation of the collateral sprouting of the messy fibres in the inner molecular layer as detected by Timm's staining. These effects were also markedly reduced by the pretreatment with MK-801. Taken together, these experiments indicate for the first time a direct relationship between the increase of GAP-43 immunostaining in the inner molecular layer of the dentate gyrus and the collateral sprouting of messy fibres in this district in response to kainic acid induced seizures. This further supports the hypothesis that the early induction of GAP-43 in granule cells may be one of the molecular mechanisms required for the synaptic reorganization of the messy fibres.

Original languageEnglish
Pages (from-to)93-101
Number of pages9
JournalEuropean Journal of Neuroscience
Volume9
Issue number1
DOIs
Publication statusPublished - 1997

Fingerprint

GAP-43 Protein
Kainic Acid
Dentate Gyrus
Seizures
Dizocilpine Maleate
Injections
N-Methyl-D-Aspartate Receptors
Silver
Hippocampus
Staining and Labeling
Messenger RNA

Keywords

  • Axon sprouting
  • Limbic seizures
  • MK-801
  • Neurodegeneration
  • NMDA receptors

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Relationship between GAP-43 expression in the dentate gyrus and synaptic reorganization of hippocampal messy fibres in rats treated with kainic acid. / Bendotti, C.; Baldessari, S.; Pende, M.; Southgate, T.; Guglimetti, F.; Samanin, R.

In: European Journal of Neuroscience, Vol. 9, No. 1, 1997, p. 93-101.

Research output: Contribution to journalArticle

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abstract = "Kainic acid-induced seizures in adult rats produce neurodegeneration in the hippocampus followed by sprouting of the messy fibres in the inner molecular layer of the dentate gyrus and changes in GAP-43 expression in the granule cells. In the present study we observed that 4 days after kainic acid injection a dense plexus of silver-impregnated degenerating terminals detected by Gallyas's method and a decrease of GAP-43 immunostaining was observed in the inner molecular layer of the dentate gyrus indicating deafferentiation of this region. This was associated with the formation of an intense GAP-43 immunostained band in the supragranular layer. MK-801, a non-competitive inhibitor of the NMDA receptor, which partially inhibited the behavioural seizures induced by KA, also protected from the inner molecular layer deafferentation and markedly reduced the expression of GAP-43 mRNA in the granule cells and the intense GAP-43 immunostained band in the supragranular layer, suggesting a relationship among these events. Two months after kainic acid injection the intense supragranular GAP-43 positive band was no longer evident but the whole inner molecular layer appeared more labelled in association with the formation of the collateral sprouting of the messy fibres in the inner molecular layer as detected by Timm's staining. These effects were also markedly reduced by the pretreatment with MK-801. Taken together, these experiments indicate for the first time a direct relationship between the increase of GAP-43 immunostaining in the inner molecular layer of the dentate gyrus and the collateral sprouting of messy fibres in this district in response to kainic acid induced seizures. This further supports the hypothesis that the early induction of GAP-43 in granule cells may be one of the molecular mechanisms required for the synaptic reorganization of the messy fibres.",
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AU - Baldessari, S.

AU - Pende, M.

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AU - Guglimetti, F.

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