Effect of Kruppel-like factor 4 on PTZ-induced acute seizure mice

• Published in: Journal of cellular and molecular medicine 2024-09, Vol.28 (17), p.e18578
• Main Authors: Li, Bingjin, Piao, Jingjing, Piao, Xinmiao, Geng, Zihui, Cheng, Ziqian, Zou, Xiaohan, Jiang, Huiyi
• Format: Article
• Language: English
• Subjects: Action potential; Alzheimer's disease; Animals; Anticonvulsants; Antiepileptic agents; Complement component C3; Convulsions & seizures; Disease Models, Animal; Drug development; Electrophysiology; Epilepsy; Gene expression; Genotype & phenotype; Glutamate receptors; Glutamatergic transmission; Hippocampus; Hippocampus - metabolism; Immunofluorescence; KLF4 protein; Kruppel-Like Factor 4 - metabolism; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Latency; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurological disorders; Original; p53 Protein; Pentylenetetrazole; Postsynaptic density; Postsynaptic density proteins; Prefrontal cortex; Prefrontal Cortex - metabolism; Protein expression; Proteins; Regeneration; Roles; Seizures; Seizures - chemically induced; Seizures - genetics; Seizures - metabolism; Transcription factors; Traumatic brain injury; Western blotting
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.18578

Kruppel-like factor 4 (Klf4) is a transcription factor that is involved in neuronal regeneration and the development of glutamatergic systems. However, it is unknown whether Klf4 is involved in acute seizure. To investigate the potential role of Klf4 in pentylenetetrazol (PTZ)-induced seizure, western blotting, immunofluorescence, behaviour test and electrophysiology were conducted in this study. We found that Klf4 protein and mRNA expression were increased in both the hippocampus (HP) and prefrontal cortex (PFC) after PTZ-induced seizure in mice. HP-specific knockout (KO) of Klf4 in mice decreased protein expression of Klf4 and the down-stream Klf4 target tumour protein 53 (TP53/P53). These molecular changes are accompanied by increased seizure latency, reduced immobility time in the forced swimming test and tail suspension test. Reduced hippocampal protein levels for synaptic proteins, including glutamate receptor 1 (GRIA1/GLUA1) and postsynaptic density protein 95 (DLG4/PSD95), were also observed after Klf4-KO, while increased mRNA levels of complement proteins were observed for complement component 1q subcomponent A (C1qa), complement component 1q subcomponent B (C1qb), complement component 1q subcomponent C (C1qc), complement component 3 (C3), complement component 4A (C4a) and complement component 4B (C4b). Moreover, c-Fos expression induced by PTZ was reduced by hippocampal conditional KO of Klf4. Electrophysiology showed that PTZ-induced action potential frequency was decreased by overexpression of Klf4. In conclusion, these findings suggest that Klf4 plays an important role in regulating PTZ-induced seizures and therefore constitutes a new molecular target that should be explored for the development of antiepileptic drugs.