Development of preventative measures against epilepsy using novel model animals (kick-in)

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659529
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Fukuoka University
• Principal Investigator: HIROSE Shinichi 福岡大学, 医学部, 教授 (60248515)
• Co-Investigator(Renkei-kenkyūsha): TAKANO Yukio 福岡大学, 薬学部, 教授 (50113246) ; SAITO Ryo 福岡大学, 薬学部, 講師 (80122696) ; KATSURABAYASHI Shutaro 福岡大学, 薬学部, 助教 (50435145)
• Project Period (FY): 2011 – 2012
• Keywords: モデル動物 / フロセミド / てんかん

Research Abstract

Dravet syndrome results from various mutations of SCN1A, the gene encoding a1 subunit of Nav1.1 channel. Microdeletion of chromosome including SCN1A leads the most severe phenotype of Dravet syndrome. We have successfully genetically engineered mice bearing a heterozygous microdeletion of Scn1a, the mouse homologue of human SCN1A. The mice exhibited severe convulsions and epileptic discharges on Electro corticogram during 4 to 8 weeks of age. We are now examining effects of NKCC1 inhibitors on the development of the phenotypes whether the inhibitors can exert a prophylactic effect. Also, we are examining the neuro-electrophysiological characteristics of the mice using the slice patch clump method on brain. Primary culture of neurons of the mice are also has been implemented.（金額単位：円）直接経費 間接経費 合 計

Research Products

• [Journal Article] A Novel Mutation of Human Liver Alanine:Glyoxylate Aminotransferase Causes Primary Hyperoxaluria Type 1:Immunohistochemical Quantification and Subcellular Distribution. (2012)
  • Author(s): Kawai C, Minatogawa Y, Akiyoshi H, Hirose S, Suehiro T, Tone S.
  • Journal Title: Acta Histochem. cytochem. Volume: 45(2) Pages: 121-9
  • DOI: doi:10.1267/ahc.11042
  • Peer Reviewed
• [Journal Article] On the likelihood of SCN1A microdeletions or duplications in Dravet syndrome withmissense mutation. (2012)
  • Author(s): Shi X, Wang J, Kurahashi H, Ishii A, Higurashi N, Kaneko S, Hirose S.
  • Journal Title: Brain Dev Volume: 34(8) Pages: 617-9
  • Peer Reviewed
• [Journal Article] Mutation of the SCN1A gene in acute encephalophathy. (2012)
  • Author(s): Saitoh M, Shinohara M, Hoshino H, Kubota M, Amemiya K, Takanashi JL, Hirose S, Mizuguchi M.
  • Journal Title: Epilepsia Volume: 53(3) Pages: 558-64
  • DOI: doi:10.1111/j.1528-1167.2011.03402.x
  • Peer Reviewed
• [Journal Article] Mutations in PRRT2 responsible for paroxysmal kinesigenic dyskinesias also cause benign familial infantile convulsions. (2012)
  • Author(s): Ono S, Yoshiura K, KinoshitaA, Kikuchi T, Nakane Y, Kato N,Sadamatsu M, Konishi T, Nagamitsu S, Matsuura M, Yasuda A, KomineM, Kanai K, Inoue T, Osamura T, Saito K, Hirose S, Koide H,Tomita H, Ozawa H, Niikawa N and Kurotaki N.
  • Journal Title: J Hum Genet Volume: 57(5) Pages: 338-41
  • DOI: doi:10.1038/jhg.2012.23
  • Peer Reviewed
• [Journal Article] PCDH19 Mutation in Japanese Females with Epilepsy. (2012)
  • Author(s): Higurashi N, Shi X, Yasumoto S, Oguni H,Sakauchi M, Itomi K, Miyamoto A, Shiraishi H, Kato T, Makita Y, Hirose S.
  • Journal Title: Epilepsy Res Volume: 99 Pages: 28-37
  • DOI: DOI:10.1016/j.eplepsyres.2011.10.014
  • Peer Reviewed
• [Journal Article] Clinical spectrum of SCN2A mutations. (2012)
  • Author(s): Shi X, Yasumoto S, Kurahashi K,Nakagawa E, Fukasawa T, Uchiya S, Hirose S.
  • Journal Title: Brain Dev Volume: 34(7) Pages: 541-5
  • DOI: doi:10.1016/j.braindev.2011.09.016
  • Peer Reviewed
• [Journal Article] A boy with a severe phenotype of succinic semialdehyde dehydrogenase deficiency. (2012)
  • Author(s): Yamakawa Y, Nakazawa T, Ishida A, Saito N, Komatsu M, Matsubara T, Obinata K, Hirose S, Okumura A, Shimizu T.
  • Journal Title: Brain Dev Volume: 34(2) Pages: 107-12
  • DOI: doi:10.1016/j.braindev.2011.05.003
  • Peer Reviewed
• [Journal Article] Early-onset absence epilepsy at eight months of age. (2011)
  • Author(s): Kobayashi Y, Akasaka N, Ohashi T,Saitoh S, Tomonoh Y, Hirose S, Tohyama J.
  • Journal Title: Epileptic Disord Volume: 13(4) Pages: 417-21
  • Peer Reviewed
• [Journal Article] Autosomal dominant nocturnal frontal lobe epilepsy: a genotypic comparative study of Japanese and Korean families carrying the CHRNA4 Ser284Leu mutation. (2011)
  • Author(s): Hwang SK, Makita Y, Kurahashi H, Cho YW, Hirose S.
  • Journal Title: J Hum Genet Volume: 56(8) Pages: 609-12
  • DOI: doi:10.1111/j.1528-1167.2011.03002.x
  • Peer Reviewed
• [Journal Article] Retrospectivemultiinstitutional study of the prevalence of early death in Dravet syndrome. (2011)
  • Author(s): Sakauchi M,Oguni H, Kato I, Osawa M, Hirose S, Kaneko S, Takahashi Y, Takayama R, Fujiwara T.
  • Journal Title: Epilepsia Volume: 52(6) Pages: 1144-9
  • DOI: doi:10.1111/j.1528-1167.2011.03053.x
  • Peer Reviewed
• [Journal Article] Mortality in Dravet syndrome: search for risk factorsin Japanese patients. (2011)
  • Author(s): Sakauchi M, Oguni H, Kato I, Osawa M, Hirose S, Kaneko S, Takahashi Y, Takayama R, Fujiwara T.
  • Journal Title: Epilepsia Volume: 52 Suppl 2 Pages: 50-4
  • DOI: doi:10.1111/j.1528-1167.2011.03002.x
  • Peer Reviewed
• [Journal Article] Diagnosing nocturnal frontal lobe epilepsy: A case study of two children. (2011)
  • Author(s): Tomonoh Y, Yasumoto S, Ihara Y, FujitaT, Nakamura N, Ninomiya S, Kodama R, Ideguchi H, Inoue T, Mitsudome A,Hirose S.
  • Journal Title: Seizure Volume: 20(7) Pages: 583-5
  • DOI: doi:10.1016/j.seizure.2011.03.004
  • Peer Reviewed
• [Journal Article] The Developmental Changes of Na(v)1.1 and Na(v)1.2 Expression in the Human Hippocampus and Temporal Lobe. (2011)
  • Author(s): Wang W, Takashima S, Segawa Y, Itoh M, Shi X, Hwang SK, Nabeshima K, Takeshita M, Hirose S.
  • Journal Title: Brain Res Volume: 1389(5) Pages: 61-70
  • DOI: doi:10.1016/j.brainres.2011.02.083
  • Peer Reviewed
• [Journal Article] Genetic testing in the epilepsies?Report of the ILAE (2011)
  • Author(s): Ottman R, Hirose S,Jain S, Lerche H, Lopes-Cendes I, Noebels JL, Serratosa J, Zara F, Scheffer IE.
  • Journal Title: Genetics Commission Epilepsia Volume: 51(4) Pages: 655-670
  • DOI: doi:10.1111/j.1528-1167.2009.02429.x
  • Peer Reviewed
• [Journal Article] Positive association between benign familial infantile convulsions and LGI4. (2010)
  • Author(s): Ishii A, Zhang B, Kaneko S, Hirose S.
  • Journal Title: Brain Dev Volume: 32 Pages: 538-43
  • DOI: doi:10.1016/j.braindev.2009.09.006
  • Peer Reviewed
• [Journal Article] IgG subclasses and complementpathway in segmental and global membranous nephropathy. (2010)
  • Author(s): Segawa Y, Hisano S, Matsushita M, Fujita T, Hirose S, Takeshita M, Iwasaki H.
  • Journal Title: Pediatr Nephrol Volume: 25(6) Pages: 1091-9
  • DOI: doi 10.1007/s00467-009-1439-8 doi:10.1016/j.eplepsyres.2008.12.003
  • Peer Reviewed
• [Presentation] Identification of ATP1A3 mutations by exome sequencing as the cause of AHC in japanese patients (2012)
  • Author(s): Ishii A,Hirose S.
  • Organizer: symposium ATP1A3 in disease from gene mutations to new treatments
  • Place of Presentation: Brussels,Belglum-
  • Year and Date: 20121210-11
• [Presentation] Genetics of benign neonatal seizures (2012)
  • Author(s): Hirose S.
  • Organizer: 12th international child Neurology Congress of Child Nuerology
  • Place of Presentation: Brisbane,Australia
  • Year and Date: 20120527-0601
• [Presentation] Neutral Hyperexcitability and the Effects of KCNQ Channel Openers on Pentylenetetrazole Induced Seizures on Mice in BFNS (2012)
  • Author(s): Tomonoh Y,Saito R,Araki K,Deshimaru M,Takano Y,Hirose S.
  • Organizer: 12th international child Neurology Congress of Child Nuerology
  • Place of Presentation: Brisbane,Australia
  • Year and Date: 20120527-0601
• [Presentation] Genetic analysis of Alternating Childhood (2012)
  • Author(s): Ishii A,saito Y,Sasaki M,Hirose S.
  • Organizer: 10th European Congress of Epileptology
  • Place of Presentation: London,UK
  • Year and Date: 2012-09-30
• [Presentation] Genetic analysis of PRRT2 for benign infantile epilepsy, infantile convulsions with choleoathetosis syndrom,and benign convulsions with mild gastroenteritis (2012)
  • Author(s): Ishii A,Yasumoto S,Ihara Y, Inoue T,Fujita T,Nakamura N,Ohfu M,Lee WT,Kaneko S, Hirose S.
  • Organizer: 2012Korea Epilepsy congress
  • Place of Presentation: Incheon,Korea
  • Year and Date: 2012-06-08
• [Presentation] The development of the DNA chip which aimed at the clinical application in epilepsy (2011)
  • Author(s): Sugawara T,Yoshida S, Wda K, Hirose S, Iwasa H,Kaneko S.
  • Organizer: 29th International Epilepsy Congress.
  • Place of Presentation: Rome
  • Year and Date: 20110828-0901
• [Presentation] Steroid pulse therapy as an effective treatment for refractory epilepsy in children with glutamate receptor (GLUR) antibodies (2011)
  • Author(s): Yasumoto S, Ihara Y, Fujita T, Tomonoh Y, Ninomiya S, Nakamura N, Ideguchi H, Inoue T, Takahashi Y, Hirose S.
  • Organizer: 29thInternational Epilepsy Congress
  • Place of Presentation: Rome
  • Year and Date: 20110828-0901
• [Presentation] Autosomal Dominant nocturnal frontal Lobe Epilepsy:A Genotypic Comparative Study of Japanese and Korean Families Carrying the CHRNA4Ser284LeuMutation (2011)
  • Author(s): Su-Kyeong Hwang,Makita Y,Kurahashi H, Yong-Won Cho, Hirose S.
  • Organizer: KES 韓国てんかん学会
  • Place of Presentation: 韓国
  • Year and Date: 2011-06-24
• [Presentation] Guideline for genetic diagnosis for epilepsy (2011)
  • Author(s): Hirose s.
  • Organizer: KES 韓国てんかん学会
  • Place of Presentation: 韓国
  • Year and Date: 2011-06-24
• [Presentation] Update for genetics of epilepsy Basic Science Session (2011)
  • Author(s): Hirose S.
  • Organizer: KES韓国てんかん学会
  • Place of Presentation: 韓国
  • Year and Date: 2011-06-24
• [Book] Jesper's Basic Mechanisms of the Epilepsies (2012)
  • Author(s): Steinlein andOK, Kaneko S, HiroseS
  • Total Pages: 1-15
  • Publisher: Nicotinic acwtycholine receptor mutations
• [Remarks]
  • URL: http://www.med.fukuoka-u.ac.jp/epilepsy/