title: Ketogenic diet decreases the level of proenkephalin mRNA induced by kainic acid in the mouse hippocampus.
abstract: The ketogenic diet (KD) has been used to control medically refractory epilepsy in children for more than 80 years. Despite the clinical efficacy of the KD, its underlying bases are still obscure. Previous work from our laboratory has established that the KD has an antiepileptic and neuroprotective effect in the kainic acid (KA)-induced seizure model. The neuronal excitation caused by KA leads to increases in the expression of a variety of genes, including immediate-early genes and opioid peptides derived from proenkephalin (PENK) and prodynorphin (PDYN). In particular, the up-regulated PENK gene that is induced by KA in the hippocampal dentate granule cells has proconvulsant properties. PENK is regulated by the c-jun amino-terminal kinase (JNK) signaling pathway, the crucial role of which is involved in the regulation of transcription factors, such as Jun and Fos. In the present study, we examined the effect of the KD on the increase of PENK, Fos, Jun, AP-1 DNA-binding activity and JNK gene expression induced by KA in the mouse hippocampus. Using in situ hybridization and northern blot analysis, we found that the KD significantly decreases the level of PENK gene expression induced by KA of the granular cells in the hippocampus. In addition, we have also found that KD diminished KA-induced AP-1 DNA-binding activity, Fos and Jun expression, and phoshorylated form of the three types of JNKs. These results suggest that the KD suppresses KA-induced activation of JNK signaling pathways, followed by a decrease of PENK gene expression in the hippocampus, thereby resulting in antiepileptic effects.
authors.affiliation: Department of Anatomy and Neurobiology, Institute of Health Science, College of Medicine, Gyeongsang National University, Jinju, Kyungnam 660-751, South Korea.
authors.forename: Hae Sook
authors.initials: HS
authors.lastname: Noh
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Gyeong Jae
authors.initials: GJ
authors.lastname: Cho
authors.forename: Wan Sung
authors.initials: WS
authors.lastname: Choi
mesh_terms: D000818:Animals; D050528:Diet, Carbohydrate-Restricted / Q000379:methods*; D018753:Diet, Protein-Restricted / Q000379:methods*; D004041:Dietary Fats / Q000008:administration & dosage*; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D004041:Dietary Fats; D004745:Enkephalins; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C029992:proenkephalin; D007608:Kainic Acid