title: Altered functional efficacy of hippocampal interneuron during epileptogenesis following febrile seizures.
abstract: Febrile seizure (FS) is the most common seizure type in infants and young children. FS may induce functional changes in the hippocampal circuitries. Abnormality of excitatory and inhibitory neurotransmissions was previously related to wide-spread seizure attack in the hippocampus following recurrent seizure onset. To clarify the involvement of expressional changes and functional alterations of hippocampal interneurons with epileptogenesis following FS, we investigated long-term effects following recurrent seizure in a hyperthermia-induced seizure animal model. At 12 weeks following FS, the recurrent seizure time period, local field potentials (LFP) revealed high amplitude potential and a sharp wave characteristic of epilepsy. Mossy fiber reorganization in the hippocampus was also detected as abnormal synaptic connection at 8 weeks. Calretinin (CR) -positive interneurons were transiently enhanced during epileptogenic period at 7-9 weeks after FS in the CA1 and DG region and it is double labeled with VGLUT-1. However, although GABAA-α1 immunoreactivities were un-changed as similar to control hippocampus at 7-9 weeks after seizure onset, its expression was significantly enhanced at 4 weeks and 12 weeks and it is colocalized with GABA. Furthermore, the field excitatory postsynaptic potential (fEPSP) and the paired-pulse responses including population spike (PS) latency, excitability ratio and PS2/PS1 ratio were markedly altered in the CA1 and DG region at 12 weeks after FS. Therefore, our findings in present study indicate that these time-dependent changes may be based on the persistent alterations of hippocampal neuronal circuits in balance between excitatory and inhibitory responses, and may lead to the epileptogenesis and spread of seizure activity following FS.
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, Chungcheongnam-Do, 31151, Republic of Korea.
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Yu
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, Chungcheongnam-Do, 31151, Republic of Korea.
authors.forename: Kahyun
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, Chungcheongnam-Do, 31151, Republic of Korea.
authors.forename: Dal Sik
authors.initials: DS
authors.lastname: Sin
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, Chungcheongnam-Do, 31151, Republic of Korea.
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, Chungcheongnam-Do, 31151, Republic of Korea. Electronic address: mdeornfl@sch.ac.kr.
authors.forename: Dae-Kyoon
authors.initials: DK
authors.lastname: Park
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, Chungcheongnam-Do, 31151, Republic of Korea. Electronic address: dskim@sch.ac.kr.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004827:Epilepsy / Q000378:metabolism; D018683:Excitatory Amino Acid Agents / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018682:GABA Agents / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000503:physiopathology; D007395:Interneurons / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism; D012640:Seizures / Q000378:metabolism / Q000503:physiopathology*; D003294:Seizures, Febrile / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018683:Excitatory Amino Acid Agents; D018682:GABA Agents; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D018698:Glutamic Acid
keywords: Calretinin; Epileptogenesis; Febrile seizure; Field excitatory postsynaptic potential; GABA(A)-α1; Paired-pulse response