Gene expression analysis of the emergence of epileptiform activity after focal injection of kainic acid into mouse hippocampus

Dario Motti, Caroline Le Duigou, Emmanuel Eugène, Nicole Chemaly, Lucia Wittner, Dejan Lazarevic, Helena Krmac, Troels Marstrand, Eivind Valen, Remo Sanges, Elia Stupka, Albin Sandelin, Enrico Cherubini, Stefano Gustincich, Richard Miles

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We report gene profiling data on genomic processes underlying the progression towards recurrent seizures after injection of kainic acid (KA) into the mouse hippocampus. Focal injection enabled us to separate the effects of proepileptic stimuli initiated by KA injection. Both the injected and contralateral hippocampus participated in the status epilepticus. However, neuronal death induced by KA treatment was restricted to the injected hippocampus, although there was some contralateral axonal degeneration. We profiled gene expression changes in dorsal and ventral regions of both the injected and contralateral hippocampus. Changes were detected in the expression of 1526 transcripts in samples from three time-points: (i) during the KA-induced status epilepticus, (ii) at 2 weeks, before recurrent seizures emerged, and (iii) at 6 months after seizures emerged. Grouping genes with similar spatio-temporal changes revealed an early transcriptional response, strong immune, cell death and growth responses at 2 weeks and an activation of immune and extracellular matrix genes persisting at 6 months. Immunostaining for proteins coded by genes identified from array studies provided evidence for gliogenesis and suggested that the proteoglycan biglycan is synthesized by astrocytes and contributes to a glial scar. Gene changes at 6 months after KA injection were largely restricted to tissue from the injection site. This suggests that either recurrent seizures might depend on maintained processes including immune responses and changes in extracellular matrix proteins near the injection site or alternatively might result from processes, such as growth, distant from the injection site and terminated while seizures are maintained.

Original languageEnglish
Pages (from-to)1364-1379
Number of pages16
JournalEuropean Journal of Neuroscience
Volume32
Issue number8
DOIs
Publication statusPublished - Oct 2010

Fingerprint

Kainic Acid
Hippocampus
Gene Expression
Injections
Seizures
Status Epilepticus
Genes
Biglycan
Extracellular Matrix Proteins
Proteoglycans
Growth
Neuroglia
Astrocytes
Cicatrix
Extracellular Matrix
Cell Death
Proteins

Keywords

  • Epilepsy
  • Gene profile
  • Hippocampus
  • Kainate

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Gene expression analysis of the emergence of epileptiform activity after focal injection of kainic acid into mouse hippocampus. / Motti, Dario; Le Duigou, Caroline; Eugène, Emmanuel; Chemaly, Nicole; Wittner, Lucia; Lazarevic, Dejan; Krmac, Helena; Marstrand, Troels; Valen, Eivind; Sanges, Remo; Stupka, Elia; Sandelin, Albin; Cherubini, Enrico; Gustincich, Stefano; Miles, Richard.

In: European Journal of Neuroscience, Vol. 32, No. 8, 10.2010, p. 1364-1379.

Research output: Contribution to journalArticle

Motti, D, Le Duigou, C, Eugène, E, Chemaly, N, Wittner, L, Lazarevic, D, Krmac, H, Marstrand, T, Valen, E, Sanges, R, Stupka, E, Sandelin, A, Cherubini, E, Gustincich, S & Miles, R 2010, 'Gene expression analysis of the emergence of epileptiform activity after focal injection of kainic acid into mouse hippocampus', European Journal of Neuroscience, vol. 32, no. 8, pp. 1364-1379. https://doi.org/10.1111/j.1460-9568.2010.07403.x
Motti, Dario ; Le Duigou, Caroline ; Eugène, Emmanuel ; Chemaly, Nicole ; Wittner, Lucia ; Lazarevic, Dejan ; Krmac, Helena ; Marstrand, Troels ; Valen, Eivind ; Sanges, Remo ; Stupka, Elia ; Sandelin, Albin ; Cherubini, Enrico ; Gustincich, Stefano ; Miles, Richard. / Gene expression analysis of the emergence of epileptiform activity after focal injection of kainic acid into mouse hippocampus. In: European Journal of Neuroscience. 2010 ; Vol. 32, No. 8. pp. 1364-1379.
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