TY - JOUR

T1 - Gene expression analysis of the emergence of epileptiform activity after focal injection of kainic acid into mouse hippocampus

AU - Motti, Dario

AU - Le Duigou, Caroline

AU - Eugène, Emmanuel

AU - Chemaly, Nicole

AU - Wittner, Lucia

AU - Lazarevic, Dejan

AU - Krmac, Helena

AU - Marstrand, Troels

AU - Valen, Eivind

AU - Sanges, Remo

AU - Stupka, Elia

AU - Sandelin, Albin

AU - Cherubini, Enrico

AU - Gustincich, Stefano

AU - Miles, Richard

N1 - © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

U2 - 10.1111/j.1460-9568.2010.07403.x

DO - 10.1111/j.1460-9568.2010.07403.x

M3 - Journal article

C2 - 20950280

VL - 32

SP - 1364

EP - 1379

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 8

ER -