Mice lacking connective tissue growth factor in the forebrain exhibit delayed seizure response, reduced c-fos expression and different microglial phenotype following acute ptz injection

Pei Fen Siow, Chih Yu Tsao, Ho Ching Chang, Chwen Yu Chen, I. Shing Yu, Kuang Yung Lee*, Li Jen Lee*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

6 Scopus citations

Abstract

Connective tissue growth factor (CTGF) plays important roles in the development and regeneration of the connective tissue, yet its function in the nervous system is still not clear. CTGF is expressed in some distinct regions of the brain, including the dorsal endopiriform nucleus (DEPN) which has been recognized as an epileptogenic zone. We generated a forebrain-specific Ctgf knockout (FbCtgf KO) mouse line in which the expression of Ctgf in the DEPN is eliminated. In this study, we adopted a pentylenetetrazole (PTZ)-induced seizure model and found similar severity and latencies to death between FbCtgf KO and WT mice. Interestingly, there was a delay in the seizure reactions in the mutant mice. We further observed reduced c-fos expression subsequent to PTZ treatment in the KO mice, especially in the hippocampus. While the densities of astrocytes and microglia in the hippocampus were kept constant after acute PTZ treatment, microglial morphology was different between genotypes. Our present study demonstrated that in the FbCtgf KO mice, PTZ failed to increase neuronal activity and microglial response in the hippocampus. Our results suggested that inhibition of Ctgf function may have a therapeutic potential in preventing the pathophysiology of epilepsy.

Original languageEnglish
Article number4921
Pages (from-to)1-14
Number of pages14
JournalInternational Journal of Molecular Sciences
Volume21
Issue number14
DOIs
StatePublished - 02 07 2020

Bibliographical note

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Endopiriform nucleus
  • Gene knockout mice
  • Hippocampus
  • Neuronal activity
  • PTZ-induced seizure

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