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

• Published in: International journal of molecular sciences Vol. 21; no. 14; p. 4921
• Main Authors: Siow, Pei-Fen, Tsao, Chih-Yu, Chang, Ho-Ching, Chen, Chwen-Yu, Yu, I-Shing, Lee, Kuang-Yung, Lee, Li-Jen
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.07.2020; MDPI
• Subjects: Animals; Anticonvulsants; Astrocytes; Astrocytes - drug effects; Astrocytes - physiology; c-Fos protein; Cell Count; Claustrum - drug effects; Claustrum - metabolism; Connective tissue; Connective tissue growth factor; Connective Tissue Growth Factor - deficiency; Connective Tissue Growth Factor - physiology; Convulsants - toxicity; Convulsions & seizures; endopiriform nucleus; Epilepsy; Forebrain; Gene Expression Regulation - drug effects; gene knockout mice; Genes, fos; Genotypes; Growth factors; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; Microglia - drug effects; Microglia - physiology; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Nervous system; neuronal activity; Pentylenetetrazole; Pentylenetetrazole - toxicity; Phenotypes; Prosencephalon - drug effects; Prosencephalon - metabolism; Proteins; Proto-Oncogene Proteins c-fos - biosynthesis; Proto-Oncogene Proteins c-fos - genetics; PTZ-induced seizure; Regeneration; Rodents; Seizures; Seizures - chemically induced; Seizures - genetics; Seizures - pathology; Seizures - physiopathology; hippocampus; gene knockout mice; endopiriform nucleus; neuronal activity; PTZ-induced seizure
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21144921

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 knockout (Fb 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 Fb 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 Fb 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.