Epileptogenesis and chronic seizures in a mouse model of temporal lobe epilepsy are associated with distinct EEG patterns and selective neurochemical alterations in the contralateral hippocampus

Dimitrula Arabadzisz, K. Antal, Franziska Parpan, Z. Emri, Jean Marc Fritschy

Research output: Contribution to journalArticle

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Abstract

Major aspects of temporal lobe epilepsy (TLE) can be reproduced in mice following a unilateral injection of kainic acid into the dorsal hippocampus. This treatment induces a non-convulsive status epilepticus and acute lesion of CA1, CA3c and hilar neurons, followed by a latent phase with ongoing ipsilateral neuronal degeneration. Spontaneous focal seizures mark the onset of the chronic phase. In striking contrast, the ventral hippocampus and the contralateral side remain structurally unaffected and seizure-free. In this study, functional and neurochemical alterations of the contralateral side were studied to find candidate mechanisms underlying the lack of a mirror focus in this model of TLE. A quantitative analysis of simultaneous, bilateral EEG recordings revealed a significant decrease of theta oscillations ipsilaterally during the latent phase and bilaterally during the chronic phase. Furthermore, the synchronization of bilateral activity, which is very high in control, was strongly reduced already during the latent phase and the decrease was independent of recurrent seizures. Immunohistochemical analysis performed in the contralateral hippocampus of kainate-treated mice revealed reduced calbindin-labeling of CA1 pyramidal cells; down-regulation of CCK-8 and up-regulation of NPY-labeling in mossy fibers; and a redistribution of galanin immunoreactivity. These changes collectively might limit neuronal excitability in CA1 and dentate gyrus, as well as glutamate release from mossy fiber terminals. Although these functional and neurochemical alterations might not be causally related, they likely reflect long-ranging network alterations underlying the independent evolution of the two hippocampal formations during the development of an epileptic focus in this model of TLE.

Original languageEnglish
Pages (from-to)76-90
Number of pages15
JournalExperimental Neurology
Volume194
Issue number1
DOIs
Publication statusPublished - Jul 2005

Fingerprint

Temporal Lobe Epilepsy
Electroencephalography
Hippocampus
Seizures
Kainic Acid
Galanin
Calbindins
Sincalide
Status Epilepticus
Pyramidal Cells
Dentate Gyrus
Glutamic Acid
Up-Regulation
Down-Regulation
Neurons
Injections
Therapeutics

Keywords

  • Ca-binding protein
  • Dentate gyrus
  • Electroencephalography
  • Mirror focus
  • Neuropeptides
  • Seizure
  • Synchronicity
  • Temporal lobe epilepsy
  • Theta frequency

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Epileptogenesis and chronic seizures in a mouse model of temporal lobe epilepsy are associated with distinct EEG patterns and selective neurochemical alterations in the contralateral hippocampus. / Arabadzisz, Dimitrula; Antal, K.; Parpan, Franziska; Emri, Z.; Fritschy, Jean Marc.

In: Experimental Neurology, Vol. 194, No. 1, 07.2005, p. 76-90.

Research output: Contribution to journalArticle

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