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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

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 be...

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Autores principales: Siow, Pei-Fen, Tsao, Chih-Yu, Chang, Ho-Ching, Chen, Chwen-Yu, Yu, I-Shing, Lee, Kuang-Yung, Lee, Li-Jen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404259/
https://www.ncbi.nlm.nih.gov/pubmed/32664674
http://dx.doi.org/10.3390/ijms21144921
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author Siow, Pei-Fen
Tsao, Chih-Yu
Chang, Ho-Ching
Chen, Chwen-Yu
Yu, I-Shing
Lee, Kuang-Yung
Lee, Li-Jen
author_facet Siow, Pei-Fen
Tsao, Chih-Yu
Chang, Ho-Ching
Chen, Chwen-Yu
Yu, I-Shing
Lee, Kuang-Yung
Lee, Li-Jen
author_sort Siow, Pei-Fen
collection PubMed
description 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.
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spelling pubmed-74042592020-08-18 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 Siow, Pei-Fen Tsao, Chih-Yu Chang, Ho-Ching Chen, Chwen-Yu Yu, I-Shing Lee, Kuang-Yung Lee, Li-Jen Int J Mol Sci Article 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. MDPI 2020-07-12 /pmc/articles/PMC7404259/ /pubmed/32664674 http://dx.doi.org/10.3390/ijms21144921 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Siow, Pei-Fen
Tsao, Chih-Yu
Chang, Ho-Ching
Chen, Chwen-Yu
Yu, I-Shing
Lee, Kuang-Yung
Lee, Li-Jen
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404259/
https://www.ncbi.nlm.nih.gov/pubmed/32664674
http://dx.doi.org/10.3390/ijms21144921
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