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Gene expression analysis of the emergence of epileptiform activity after focal injection of kainic acid into mouse hippocampus
Author(s) -
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
Publication year - 2010
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07403.x
Subject(s) - status epilepticus , kainic acid , hippocampus , epilepsy , epileptogenesis , neuroscience , extracellular matrix , biology , immediate early gene , gene expression , pathology , microbiology and biotechnology , medicine , gene , genetics , glutamate receptor , receptor
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.