Kainic acid-induced convulsions cause prolonged changes in the chondroitin sulfate proteoglycans neurocan and phosphacan in the limbic structures

Motoi Okamoto, Junko Sakiyama, Shuji Mori, Sekiko Kurazono, Shinich Usui, Masumi Hasegawa, Atsuhiko Oohira

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Systemic administration of kainic acid induces repeated convulsive seizures (KA convulsions) that result in neuropathological changes similar to temporal lobe epilepsy and the appearance of spontaneous recurrent seizures (SRS). The appearance of SRS is considered a result of the remodeling of neuronal networks following neuronal degeneration. We investigated the changes in chondroitin sulfate proteoglycans (CSPGs) in the limbic structures after KA convulsions in the rat using monoclonal antibodies 1G2, which recognizes full-length neurocan and the C-terminal half of neurocan, neurocan C, and 6B4, which recognize phosphacan and protein tyrosine phosphatase ζ. After KA convulsions, full-length neurocan appeared by 24 h and reached a peak by 48 to 72 h, whereas phosphacan decreased within 24 h in the hippocampus. In immunohistochemistry, neurocan increased in the limbic structures coincident with the appearance of reactive astrocytes. Phosphacan decreased coincident with pyramidal cell loss in the hippocampus, and the number of phosphacan-positive perineuronal nets around parvalbumin neurons decreased, whereas parvalbumin neurons were relatively conserved. In contrast, phosphacan increased in the entorhinal and piriform cortices in correlation with the severity of neuronal loss. Both neurocan and phosphacan recovered to the control level by 8 weeks after KA convulsions in some rats, but the changes in neurocan and phosphacan described above still persisted in more than half the rats. The results indicate that KA convulsions induce prolonged changes in neurocan and phosphacan similar to those in the developing rat brain and suggest a role of these CSPGs in the remodeling of neuronal networks related to the establishment or enhancement of epileptogenesis.

Original languageEnglish
Pages (from-to)179-195
Number of pages17
JournalExperimental Neurology
Volume184
Issue number1
DOIs
Publication statusPublished - Nov 2003

Keywords

  • Chondroitin sulfate
  • Hippocampus
  • Kainic acid
  • Limbic cortices
  • Neurocan
  • Phosphacan
  • Proteoglycans
  • Temporal lobe epilepsy

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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