Exploring the development of functional disorders in central nervous system

2013 Fiscal Year Final Research Report

• Project/Area Number: 22390224
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Mie University
• Principal Investigator: OKADA Motohiro 三重大学, 医学(系)研究科(研究院), 教授 (10281916)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Noboru 三重大学, 生命科学研究支援センター, 准教授 (00202135) ; FUKUZAWA Masashi 弘前大学, 農学生命科学部, 教授 (10231557) ; SAITO Mitsuhiro 三重大学, 生命科学研究支援センター, 助教 (50303722) ; MIZOGUTI Akira 三重大学, 大学院・医学系研究科, 教授 (90181916)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Keywords: てんかん / 病態 / トランスジェニックラット

Research Abstract

Mutations of genes (CHRNA4, CHRNB2, or CHRNA2) of neuronal nicotinic ACh receptor (nAChR) cause autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) in human. ADNFLE-related seizures are seen exclusively during slow wave phase sleep. We generated transgenic rat strains that harbor a missense mutation S286L rat Chrna4 gene, which had been identified in CHRNA4 in ADNFLE with Cre gene (S286L-TG). S286L-TG was free of biological abnormalities, such as dysmorphology in CNS, and behavioral abnormalities. To clarify the effects of S286L mutantion on epileptogenesis and ictogenesis of ADNFLE, after ADNFLE onset, S286L-TG was administrated tamoxifen (Cre inducer agent). The degradation of S286L mutant Chrna4 induced by Cre did not affect ADNFLE seizures. These results suggest that S286L mutant Chrna4 gene probably plays important roles in the development of epileptogenesis, but did not affect ictogenesis.

Research Products

• [Journal Article] Zonisamide regulates basal ganglia transmission via astroglial kynurenine pathway (2014)
  • Author(s): Fukuyama, K., Tanahashi, S., Hoshikawa, M., Shinagawa, R., Okada, M.
  • Journal Title: Neuropharmacology Volume: 76 Pt A Pages: 137-145
  • DOI: 10.1016/j.neuropharm.2013.08.002
  • Peer Reviewed
• [Journal Article] Association of nonsense mutation in GABRG2 with abnormal trafficking of GABA receptors in severe epilepsy (2014)
  • Author(s): Ishii, A., Kanaumi, T., Sohda, M., Misumi, Y., Zhang, B., Kakinuma, N., Haga, Y., Watanabe, K., Takeda, S., Okada, M., Ueno, S., Kaneko, S., Takashima, S., Hirose, S.
  • Journal Title: Epilepsy Res Pages: 420-432
  • DOI: 10.1016/j.eplepsyres.2013.12.005
  • Peer Reviewed
• [Journal Article] Genexgenexgender interaction of BDNF and COMT genotypes associated with panic disorder (2014)
  • Author(s): Konishi, Y., Tanii, H., Otowa, T., Sasaki, T., Tochigi, M., Umekage, T., Motomura, E., Shiroyama, T., Kaiya, H., Okazaki, Y., Okada, M.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 51C Pages: 119-125
  • DOI: 10.1016/j.pnpbp.2014.01.020
  • Peer Reviewed
• [Journal Article] Differential mechanisms underlie the regulation of serotonergic transmission in the dorsal and median raphe nuclei by mirtazapine : a dual probe microdialysis study (2013)
  • Author(s): Fukuyama, K., Tanahashi, S., Hamaguchi, T., Nakagawa, M., Shiroyama, T., Motomura, E., Okada, M.
  • Journal Title: Psychopharmacology (Berl) Volume: 229 Pages: 617-626
  • DOI: 10.1007/s00213-013-3122-9
  • Peer Reviewed
• [Journal Article] ONO-2506 inhibits spike-wave discharges in a genetic animal model without affecting traditional convulsive tests via gliotransmission regulation (2013)
  • Author(s): Yamamura, S., Hoshikawa, M., Kato, D., Saito, H., Suzuki, N., Niwa, O., Okada, M.
  • Journal Title: Br J Pharmacol Volume: 168 Pages: 1088-1100
  • DOI: 10.1111/j.1476-5381.2012.02132.x
  • Peer Reviewed
• [Journal Article] Levetiracetam inhibits neurotransmitter release associated with CICR (2012)
  • Author(s): Fukuyama, K., Tanahashi, S., Nakagawa, M., Yamamura, S., Motomura, E., Shiroyama, T., Tanii, H., Okada, M.
  • Journal Title: Neurosci Lett Volume: 518 Pages: 69-74
  • DOI: 10.1016/j.neulet.2012.03.056
  • Peer Reviewed
• [Journal Article] The development of agoraphobia is associated with the symptoms and location of a patient's first panic attack (2012)
  • Author(s): Hara, N., Nishimura, Y., Yokoyama, C., Inoue, K., Nishida, A., Tanii, H., Okada, M., Kaiya, H., Okazaki, Y.
  • Journal Title: Biopsychosoc Med Volume: 6 Pages: 12
  • DOI: 10.1186/1751-0759-6-12
  • Peer Reviewed
• [Journal Article] Electroencephalographic dipole source modeling of frontal intermittent rhythmic delta activity (2012)
  • Author(s): Motomura, E., Inui, K., Ohoyama, K., Nishimura, Y., Nakagawa, M., Maeda, M., Matsushima, N., Ushiro, K., Suzuki, D., Kakigi, R., Okada, M.
  • Journal Title: Neuropsychobiology Volume: 65 Pages: 103-108
  • DOI: 10.1159/000330011
  • Peer Reviewed
• [Journal Article] Lamotrigine-induced neuroleptic malignant syndrome under risperidone treatment : a case report (2012)
  • Author(s): Motomura, E., Tanii, H., Usami, A., Ohoyama, K., Nakagawa, M., Okada, M.
  • Journal Title: J Neuropsychiatry Clin Neurosci Volume: 24 Pages: E38-39
  • DOI: 10.1176/appi.neuropsych.11040093
  • Peer Reviewed
• [Journal Article] Combination Therapy of Zonisamide With Aripiprazole on ECT- and Benzodiazepine-Resistant Periodic Catatonia (2012)
  • Author(s): Nakagawa, M., Yamamura, S., Motomura, E., Tanii, H., Okada, M.
  • Journal Title: J Neuropsychiatry Clin Neurosci Volume: 24 Pages: E9-10
  • DOI: 10.1176/appi.neuropsych.11040093
  • Peer Reviewed
• [Journal Article] Memory-based pre-attentive auditory N1 elicited by sound movement (2012)
  • Author(s): Ohoyama, K., Motomura, E., Inui, K., Nishihara, M., Otsuru, N., Oi, M., Kakigi, R., Okada, M.
  • Journal Title: Neurosci Res Volume: 73 Pages: 248-251
  • DOI: 10.1016/j.neures.2012.04.003
  • Peer Reviewed
• [Journal Article] Hyperpolarization-activated cyclic nucleotide gated channels : a potential molecular link between epileptic seizures and Abeta generation in Alzheimer's disease (2012)
  • Author(s): Saito, Y., Inoue, T., Zhu, G., Kimura, N., Okada, M., Nishimura, M., Kimura, N., Murayama, S., Kaneko, S., Shigemoto, R., Imoto, K., Suzuki, T.
  • Journal Title: Mol Neurodegeneration Volume: 7
  • DOI: 10.1186/1750-1326-1187-1150(S0304-3940(12)00440-5[pii]10.1016/j.neulet.2012.03.056)
  • Peer Reviewed
• [Journal Article] Novel delta1-receptor agonist KNT-127 increases the release of dopamine and L-glutamate in the striatum, nucleus accumbens and median pre-frontal cortex (2012)
  • Author(s): Tanahashi, S., Ueda, Y., Nakajima, A., Yamamura, S., Nagase, H., Okada, M.
  • Journal Title: Neuropharmacology Volume: 62 Pages: 2057-2067
  • DOI: 10.1016/j.neuropharm.2012.01.005
  • Peer Reviewed
• [Journal Article] Effect of lamotrigine and carbamazepine on corticotropin-releasing factor-associated serotonergic transmission in rat dorsal raphe nucleus (2012)
  • Author(s): Tanahashi, S., Yamamura, S., Nakagawa, M., Motomura, E., Okada, M.
  • Journal Title: Psychopharmacology (Berl) Volume: 220 Pages: 599-610
  • DOI: 10.1007/s00213-011-2506-y
  • Peer Reviewed
• [Journal Article] Dopamine D2 and serotonin 5-HT1A receptors mediate the actions of aripiprazole in mesocortical and mesoaccumbens transmission (2012)
  • Author(s): Tanahashi, S., Yamamura, S., Nakagawa, M., Motomura, E., Okada, M
  • Journal Title: Neuropharmacology Volume: 62 Pages: 765-774
  • DOI: 10.1016/j.neuropharm.2011.08.031
  • Peer Reviewed
• [Journal Article] Clozapine, but not haloperidol, enhances glial D-serine and L-glutamate release in rat frontal cortex and primary cultured astrocytes (2012)
  • Author(s): Tanahashi, S., Yamamura, S., Nakagawa, M., Motomura, E., Okada, M.
  • Journal Title: Br J Pharmacol Volume: 165 Pages: 1543-1555
  • DOI: 10.1111/j.1476-5381.2011.01638.x
  • Peer Reviewed
• [Journal Article] Dysfunction of extrasynaptic GABAergic transmission in phospholipase C-related, but catalytically inactive protein 1 knockout mice is associated with an epilepsy phenotype (2012)
  • Author(s): Zhu, G., Yoshida, S., Migita, K., Yamada, J., Mori, F., Tomiyama, M., Wakabayashi, K., Kanematsu, T., Hirata, M., Kaneko, S., Ueno, S., Okada, M
  • Journal Title: J Pharmacol Exp Ther Volume: 340 Pages: 520-528
  • DOI: 10.1124/jpet.111.182386
  • Peer Reviewed
• [Journal Article] Effect of novel atypical antipsychotic, blonanserin, on extracellular neurotransmitter level in rat prefrontal cortex (2011)
  • Author(s): Ohoyama, K., Yamamura, S., Hamaguchi, T., Nakagawa, M., Motomura, E., Shiroyama, T., Tanii, H., Okada, M.
  • Journal Title: Eur J Pharmacol Volume: 653 Pages: 47-57
  • DOI: 10.1016/j.ejphar.2010.11.023
  • Peer Reviewed
• [Journal Article] Different actions for acute and chronic administration of mirtazapine on serotonergic transmission associated with raphe nuclei and their innervation cortical regions (2011)
  • Author(s): Yamamura, S., Abe, M., Nakagawa, M., Ochi, S., Ueno, S., Okada, M.
  • Journal Title: Neuropharmacology Volume: 60 Pages: 550-560
  • DOI: 10.1016/j.neuropharm.2010.12.025
  • Peer Reviewed
• [Journal Article] Generation of epilepsy animal model bearing a genetic abnormality identified in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) of humans. Jpn. J (2010)
  • Author(s): Okada, M.
  • Journal Title: Neuropsychopharmacol Volume: 30 Pages: 9-14
  • Peer Reviewed
• [Presentation] 新たな治療標的としてのグリア伝達 (2013)
  • Author(s): 岡田 元宏
  • Organizer: 47回日本てんかん学会学術集会
  • Place of Presentation: 北九州国際会議場
  • Year and Date: 2013-10-11
• [Presentation] 「個別化治療up to date : 遺伝子診断の現状と治療への応用」(指定討論) (2012)
  • Author(s): 岡田 元宏
  • Organizer: 46回日本てんかん学会 学術集会
  • Place of Presentation: 都市センターホテル
  • Year and Date: 2012-10-11