Aberrant expression of PAR bZIP transcription factors is associated with epileptogenesis, focus on hepatic leukemia factor

• Published in: Scientific reports Vol. 10; no. 1; p. 3760
• Main Authors: Rambousek, Lukas, Gschwind, Tilo, Lafourcade, Carlos, Paterna, Jean-Charles, Dib, Linda, Fritschy, Jean-Marc, Fontana, Adriano
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.02.2020; Nature Publishing Group
• Subjects: 631/378/1385; 631/378/1689; 631/378/371; 692/617; 692/617/375/178; Animal models; Animals; Basic-Leucine Zipper Transcription Factors - metabolism; Circadian rhythms; Convulsions & seizures; Cytokines; Dentate gyrus; Dentate Gyrus - metabolism; Dentate Gyrus - pathology; Disease Models, Animal; Epilepsy; Epilepsy - chemically induced; Epilepsy - metabolism; Gene Expression Regulation; Hippocampus; Humanities and Social Sciences; Inflammation; Injection; Kainic acid; Kainic Acid - adverse effects; Kainic Acid - pharmacology; Leukemia; Male; Mice; multidisciplinary; Neurological diseases; Science; Science (multidisciplinary); Seizures; Temporal lobe; Transcription factors
• DOI: 10.1038/s41598-020-60638-7
• ISSN: 2045-2322

Epilepsy is a widespread neurological disease characterized by abnormal neuronal activity resulting in recurrent seizures. There is mounting evidence that a circadian system disruption, involving clock genes and their downstream transcriptional regulators, is associated with epilepsy. In this study, we characterized the hippocampal expression of clock genes and PAR bZIP transcription factors (TFs) in a mouse model of temporal lobe epilepsy induced by intrahippocampal injection of kainic acid (KA). The expression of PAR bZIP TFs was significantly altered following KA injection as well as in other rodent models of acquired epilepsy. Although the PAR bZIP TFs are regulated by proinflammatory cytokines in peripheral tissues, we discovered that the regulation of their expression is inflammation-independent in hippocampal tissue and rather mediated by clock genes and hyperexcitability. Furthermore, we report that hepatic leukemia factor ( Hlf ), a member of PAR bZIP TFs family, is invariably downregulated in animal models of acquired epilepsy, regulates neuronal activity in vitro and its overexpression in dentate gyrus neurons in vivo leads to altered expression of genes associated with seizures and epilepsy. Overall, our study provides further evidence of PAR bZIP TFs involvement in epileptogenesis and points to Hlf as the key player.