Increased expression of the lysosomal protease cathepsin S in hippocampal microglia following kainate-induced seizures

Noriyuki Akahoshi, Yoshiya L. Murashima, Toshiyuki Himi, Yasuki Ishizaki, Isao Ishii

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

To examine lesions caused by seizures in the developing brain, seizures were induced by the intraperitoneal injection of kainate and nicotine into juvenile mice. After a week, whole brain sections were examined using histochemistry and the gene expression profiles in the neocortices and hippocampi were analyzed using a DNA microarray. Propidium iodide and Fluoro-Jade C staining revealed that kainate but not nicotine-induced degeneration of the hippocampal pyramidal neurons. Comparative analyses of 12,488 probe sets on the microarray chip revealed the differential expression of 208 and 1243 probe sets in the neocortices and hippocampi of kainate-injected mice, respectively, as well as that of 535 and 436 probe sets in the neocortices and hippocampi of nicotine-injected mice, respectively, the patterns of change were largely drug-specific and region-specific. Among a variety of kainate-modified genes including those representing neurodegeneration and astrogliosis, we identified an increased gene expression of the lysosomal cysteine protease cathepsin S in the hippocampi of kainate-injected mice. Western blot analysis of the hippocampal homogenates revealed that kainate induced a 3.3-fold increase in cathepsin S expression. Immunohistochemistry using cell type-specific markers showed that cathepsin S was induced in microglia, especially those surrounding degenerating pyramidal neurons, but not in neurons themselves or astroglia, in the hippocampal CA1 region of kainate-injected mice. These results indicate that seizures induced by kainate elicit neurodegeneration, astrogliosis, and microglial activation accompanied by the expression of cathepsin S while those induced by nicotine do not.

Original languageEnglish
Pages (from-to)136-141
Number of pages6
JournalNeuroscience Letters
Volume429
Issue number2-3
DOIs
Publication statusPublished - 2007 Dec 18

Keywords

  • Astroglia
  • Cathepsin
  • Kainic acid
  • Microarray
  • Neurodegeneration
  • Seizure

ASJC Scopus subject areas

  • Neuroscience(all)

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