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 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.
['Siow|Pei-Fen|PF|0000-0003-2864-6324', 'Tsao|Chih-Yu|CY|', 'Chang|Ho-Ching|HC|', 'Chen|Chwen-Yu|CY|', 'Yu|I-Shing|IS|0000-0002-2369-5816', 'Lee|Kuang-Yung|KY|', 'Lee|Li-Jen|LJ|0000-0001-9108-3654']
D000818:Animals D001253:Astrocytes D002452:Cell Count D000079482:Claustrum D055513:Connective Tissue Growth Factor D003292:Convulsants D005786:Gene Expression Regulation D016762:Genes, fos D006624:Hippocampus D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D017628:Microglia D009419:Nerve Tissue Proteins D010433:Pentylenetetrazole D016548:Prosencephalon D016760:Proto-Oncogene Proteins c-fos D012640:Seizures
endopiriform nucleus hippocampus neuronal activity PTZ-induced seizure gene knockout mice