氏 名 高橋 悟
所 属 小児科学講座
役職名 小児科講師
専門分野 神経学
出身大学(期) 旭川医科大学(12期)
国内・国外留学など
国立精神神経センター神経研究所,米国国立衛生研究所
所属学会・
専門医
日本小児科学会(専門医)、日本小児神経学会(専門医)、日本てんかん学会
専門詳細 小児神経学
研究テーマ・内容 神経発達異常の病態解明とその治療法開発
英文業績
(1996〜2011)
  • Takahashi S, Mitamura R, Ito Y, Suzuki N, Okuno A: Hashimoto encephalopathy: Etiological considerations. Pediatr Neurol 11: 328-331, 1994
  • Saijo M, Takahashi S, Kokubo M, Saino T, Ishii F, Inyaku F, Takimoto M, Takahashi Y: The role of respiratory syncytial virus in acute bronchiolitis in small children in northern Japan. Acta Paediatr Jpn 36: 371-374, 1994
  • Takahashi S, Miyamoto A, Oki J, Azuma H, Okuno A: Acute transverse myelitis caused by ECHO virus type 18 infection. Eur J Pediatr 154: 378-380, 1995
  • Takahashi S, Miyamoto A, Oki J, Saino T, Inyaku F: Alobar holoprosencephaly with diabetes insipidus and neuronal migrational disorder. Pediatr Neurol 13: 175-177, 1995
  • Tanaka H, Takahashi S, Miyamoto A, Oki J, Cho K, Okuno A: Effects of neonatal hypoxia on brainstem cholinergic neurons - pedunculopontine nucleus and lateral tegmental nucleus -. Brain Dev 17: 264-270, 1995
  • Oki J, Yoshida H, Imanishi A, Takahashi S, Miyamoto A, Yoda M, Miura J: Serial neuroimages of acute necrotizing encephalopathy associated with human herpesvirus 6 infection. Brain Dev 1995; 17: 356-359, 1995
  • Miyamoto A, Takahashi S, Tokumitsu A, Oki J: Ictal HMPAO-single photon emission computed tomography findings in reading epilepsy in a Japanese boy. Epilepsia 36: 1161-1163, 1995
  • Takahashi S, Miyamoto A, Oki J, Okuno A: CTG trinucleotide repeat length and clinical expression in a family with myotonic dystrophy. Brain Dev 18: 127-130, 1996
  • Okamoto N, Wada Y, Kawabata H, Ishikiriyama S, Takahashi S: A novel mutation in L1CAM gene in a Japanese patient with X-linked hydrocephalus. Jpn J Human Genet 1996; 41: 431-437, 1996
  • Tanaka H, Takahashi S, Miyamoto A, Oki J, Cho K, Okuno A: Developmental changes in the noradrenergic innervations of spinal motoneurons in neonatal rats. Pediatr Neurol 14: 21-27, 1996
  • Takahashi S, Makita Y, Okamoto N, Miyamoto A, Oki J: L1CAM mutation in a Japanese family with X-linked hydrocephalus: a study for genetic counseling. Brain Dev 19: 559-562, 1997
  • Takahashi S, Oki J, Miyamoto A, Tokumitsu A, Obata M, Ogawa K, Tokusashi Y, Saijo H, Okuno A: Autopsy findings in pyruvate dehydrogenase E1a deficiency: case report. J Child Neurol 12: 519-524, 1997
  • Azuma H, Makita Y, Araki A, Miyamoto A, Tsuchida A, Takahashi S, Ooshima M, Okuno A: Elevated interleukin 6 without pleocytosis in cerebrospinal fluid in encephalitis patients. Eur J Pediatr 156: 507-508, 1997
  • Miyamoto A, Oki J, Takahashi S, Itoh J, Kusunoki Y, Cho K: Serial imaging in MELAS. Neuroradiology 39: 427-430, 1997
  • Miyamoto A, Yamamoto M, Takahashi S, Oki J: Classical Rett syndrome in sisters: variability of clinical expression. Brain
  • Dev 19: 492-494, 1997 Saijo H, Tanaka H, Ito J, Tasaki T, Cho K, Tokumitsu A, Takahashi S, Miyamoto A, Oki J: Pyruvate dehydrogenase complex deficiency with multiple minor anomalies. Acta Paediatri Jpn 39: 230-232, 1997
  • Takahashi S, Makita Y, Oki J, Miyamoto A, Yanagawa J, Naito E, Goto Y, Okuno A: De novo mtDNA nt8993 (T>G) mutation resulting in Leigh syndrome. Am J Hum Genet 62: 717-719, 1998
  • Takahashi S, Oki J, Miyamoto A, Okuno A: Hemidystonia, hemichorea and motor aphasia associated with bilateral ischemic lesions in the striatum: Regional cerebral blood flow studies to clarify the pathophysiology. J Child Neurol 13: 408-411, 1998
  • Oki J, Miyamoto A, Takahashi S, Itoh J, Sakata Y, Okuno A: Cyclic vomiting and elevation of creatine kinase associated with bitemporal hypoperfusion and EEG abnormalities: a migraine equivalent? Brain Dev 20: 186-189, 1998
  • Tanaka H, Oki J, Takahashi S, Miyamoto A, Cho K, Okuno A: Effects of neonatal hypoxia on the medulla-spinal cord descending neurons. Pediatr Neurol 19: 204-210, 1998
  • Miyamoto A, Oki J, Takahashi S, Okuno A: Serum melatonin kinetics and long-term melatonin treatment for sleep disorders in Rett syndrome. Brain Dev 21: 59-62, 1998
  • Takahashi S, Oki J, Miyamoto A, Koyano S, Ito K, Azuma H, Okuno A: Encephalopathy associated with haemophagocytic lymphohistiocytosis following rotavirus infection. Eur J Pediatr 158: 133-137, 1999
  • Takahashi S, Oki J, Miyamoto A, Okuno A: Proton magnetic resonance spectroscopy to study the metabolic changes in the brain of a patient with Leigh syndrome. Brain Dev 21: 200-204, 1999
  • Takahashi S, Oki J, Miyamoto A, Moriyama T, Asano A, Inyaku F, Okuno A: Beta-2-microglobulin and ferritin in cerebrospinal fluid for evaluation of patients with meningitis of different etiologies. Brain Dev 21: 192-199, 1999
  • Takahashi S, Tanaka H, Oki J: Development of spinal motoneurons in rats after a neonatal hypoxic insult. Pediatr Neurol 21: 715-720, 1999
  • Oki J, Miyamoto A, Takahashi S, Takei H: Cognitive deterioration associated with focal dysplasia. Pediatr Neurol 20: 73-77, 1999
  • Oki J, Takahashi S, Miyamoto A, Tachibana Y: Cerebellar hypoperfusion and developmental dysphasia in a male. Pediatr Neurol 21: 745-748, 1999
  • Takahashi S, Ohsugi K, Yamamoto T, Shiomi M, Sakuragawa N: A novel approach to ex vivo gene therapy for familial hypercholesterolemia using human amniotic epithelial cells as a transgene carrier. Tohoku J Exp Med 193: 279-292, 2001
  • Kosuga M, Takahashi S, Tanabe A, Fujino M, Li XK, Suzuki S, Yamada M, Kakishita K, Ono F, Sakuragawa N, Okuyama T: Widespread distribution of adenovirus-transduced monkey amniotic epithelial cells after local intracerebral injection: implication for cell-mediated therapy for lysosome storage disorders. Cell Transplant 10: 435-439, 2001
  • Ko J, Humbert S, Bronson RT, Takahashi S, Kulkarni AB, Li E, Tsai LH: p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment. J Neurosci 21: 6758-6771, 2001
  • Li BS, Sun MK, Zhang L, Takahashi S, Ma W, Vinade L, Kulkarni AB, Brady RO, Pant HC: Regulation of NMDA receptors by cyclin-dependent kinase-5. Proc Natl Acad Sci USA 98: 12742-12747, 2001
  • Li BS, Zhang L, Takahashi S, Ma W, Jaffe H, Kulkarni AB, Pant HC: Cyclin-dependent kinase 5 prevents neuronal apoptosis by negative regulation of c-Jun N-terminal kinase 3. EMBO J 21: 324-333, 2002
  • Ohshima T, Ogawa M, Takeuchi K, Takahashi S, Kulkarni AB, Mikoshiba K: Cyclin-dependent kinase 5/p35 contributes synergistically with Reelin/Dab1 to the positioning of facial branchiomotor and inferior olive neurons in the developing mouse hindbrain. J Neurosci 22: 4036-4044, 2002
  • Takahashi S, Saito T, Hisanaga S, Pant HC, Kulkarni AB: Tau phosphorylation by cyclin-dependent kinase 5/p39 during brain development reduces its affinity for microtubules. J Biol Chem 278: 10506-10515, 2003
  • Li BS, Ma W, Jaffe H, Zheng Y, Takahashi S, Zhang L, Kulkarni AB, Pant HC: Cdk5 is involved in neuregulin-dependent activation of PI-3 kinase and Akt activity mediating neuronal survival. J Biol Chem 278: 35702-35709, 2003
  • Takahashi S, Kulkarni AB: Mutant superoxide dismutase 1 causes motor neuron degeneration independent of cyclin-dependent kinase 5 activation by p35 or p25. J Neurochem 88: 1295-1304, 2004
  • Hirasawa M, Ohshima T, Takahashi S, Veeranna, Pant HC, Mikoshiba K, Brady RO and Kulkarni AB: Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects. Proc. Natl. Acad. Sci. USA 101:6249-6254, 2004.
  • Kesavapany S, Amin N, Zheng YL, Nijhara R, Jaffe H, Sihag R, Gutkind JS, Takahashi S, Kulkarni AB, Grant P and Pant HC: p35/cyclin-dependent kinase 5 phosphorylation of Ras guanine nucleotide releasing factor 2 (RasGRF2) mediates Rac-dependent extracellular signal-regulated kinase 1/2 activity, altering RasGRF2 and microtubule-associated protein 1b distribution in neurons.   J Neurosci 24: 4421-4431, 2004.
  • Griffin SV, Hiromura K, Pippin J, Petermann AT, Blonski MJ, Krofft R, Takahashi S, Kulkarni AB, and Shankland SJ: Cyclin-dependent kinase 5 is a regulator of podocyte differentiation, proliferation, and morphology. Am J Pathol 165: 1175-1185, 2004.
  • Takahashi S, Ohshima T, Cho A, Sreenath T, Iadarola MJ, Pant HC, Kim Y, Nairn AC, Brady RO, Greengard P and Kulkarni AB: Increased activity of cyclin-dependent kinase 5 leads to attenuation of cocaine-mediated dopamine signaling. Proc. Natl. Acad. Sci. USA 102: 1737-1742, 2005.
  • Okamoto T, Shirai M, Kokubo M, Takahashi S, Kajino M, Takase M, Sakata H and Oki J: Human milk reduces the risk of retinal detachment in extremely low birth weight infants. Pediatr Int 49: 894-897, 2007
  • Okamoto T, Takahashi S, Nakamura E, Nagaya K, Hayashi T, Shirai M, Fujieda K: Increased matrix metalloproteinase-9 activity in the cerebrospinal fluid of infants with posthemorrhagic hydrocephalus. Early Hum Dev 84(2):137-139, 2008
  • Ohinata J, Suzuki N, Araki A, Takahashi S, Fujieda K, Tanaka H: Actigraphic assessment of sleep disorders in children with chronic fatigue syndrome, Brain Dev 30: 329-333, 2008
  • Takahashi S, Ohinata J, Makita Y, Suzuki N, Araki A, Sasaki A, Murono K, Tanaka H, Fujieda K: Skewed X chromosome inactivation failed to explain the normal phenotype of a carrier female with MECP2 mutation resulting in Rett syndrome, Clin Genet 73: 257-261, 2008
  • Takahashi S, Ohinata J, Suzuki N, Amamiya S, Kajihama A, Sugai R, Araki A, Fujieda K, Tanaka H: Molecular analysis and anticonvulsant therapy in two patients with glucose transporter 1 deficiency syndrome: A successful use of zonisamide for controlling the seizures. Epilepsy Res 80: 18-22, 2008
  • Matsumoto N, Takahashi S, Toriumi N, Sarashina T, Makita Y, Tachibana Y, Fujieda K:Acute disseminated encephalomyelitis in an infant with incontinentia pigmenti. Brain Dev, 31: 625-628, 2009
  • Okamoto T, Takahashi S, Nakamura E, Nagaya K, Hayashi T, Fujieda K:Transforming growth factor-beta1 induces matrix metallpproteinase-9 expression in human meningeal cells via ERK and Smad pathways. BBRC, 383: 475-479, 2009
  • Mireguli M,Takahashi S,Okajima K,Suzuki N,Ohinata J,Araki A,Tanaka T,Mukai T, Fujieda K:Silent exonic mutation in the acd-alpha-glycosidase gene that causes glycogen storage disease type II by affecting mRNA splicing. J Hum Genet, 54: 493-496, 2009
  • Takahashi S, Ohshima T, Hirasawa M, Pareek TK, Bugge TH, Morozov A, Fujieda K, Brady RO, Kulkarni AB: Conditional deletion of neuronal cyclin-dependent kinase 5 in developing forebrain results in microglial activation and neurodegeneration. Am J Pathol 176: 320-329, 2010
  • Tanaka H, Amamiya S, Takahashi S, Suzuki N, Araki A, Ohinata J, Fujieda K: Effect of neonatal hypoxia on the development of intraspinal serotonergic fibers in relation to spinal motoneurons. Brain Dev 32: 268-274, 2010
  • Muto A, Oguni H, Takahashi Y, Shirasaka Y, Sawaishi Y, Yano T, Hoshida T, Osaka H, Nakasu S, Akasaka N, Sugai K, Miyamoto A, Takahashi S, Suzuki M, Ohmori I, Nabatame S, Osawa M: Nationwide survey (incidence, clinical course, prognosis) of Rasmussen’s encephalitis. Brain Dev 32: 445-453, 2010
  • Okamoto T, Takahashi S, Nakamura E, Nagaya K, Hayashi T, Shirai M, Fujieda K: Increased expression of matrix metalloproteinase-9 and hepatocyte growth factor in the cerebrospinal fluid of infants with posthemorrhagic hydrocephalus. Early Hum Dev 86: 251-254, 2010
  • Zheng YL, Li BS, Rudrabhatla P, Shukla V, Amin ND, Maric D, Kesavapany S, Kanungo J, Pareek TK, Takahashi S, Grant P, Kulkarni AB, Pant HC: Phosphorylation of p27Kip1 at Thr187 by Cyclin-dependent Kinase 5 Modulates Neural Stem Cell Differentiation. Mol Biol Cell 21: 3601-3614, 2010
  • He X, Takahashi S, Suzuki H, Hashikawa T, Kulkarni AB, Mikoshiba K, Ohshima T: Hypomyelination phenotype caused by impaired differentiation of oligodendrocytes in Emx1-cre mediated Cdk5 conditional knockout mice. Neurochem Res 36: 1293-1303, 2011
  • Tachi N, Takahashi S, Jo M, Shinoda M: A new mutation of GCH1 in triplets family with dopa-responsive dystonia. Eur J Neurol 18: 1191-1193, 2011
  • Hara M, Nishi Y, Yamashita Y, Yoh J, Takahashi S, Nagamitsu SI, Kakuma T, Hosoda H, Kangawa K, Kojima M, Matsuishi T: Ghrelin levels are reduced in Rett syndrome patients with eating difficulties. Int J Dev Neurosci 29: 899-902, 2011
  • Kitamura Y, Okumura A, Hayashi M, Mori H, Takahashi S, Yanagihara K, Miyata R, Tanuma N, Mimaki T, Abe S, Shimizu T: Oxidative stress markers and phosphorus magnetic resonance spectroscopy in a patient with GLUT1 deficiency treated with modified Atkins diet. Brain Dev 2011 (in press)
  • Takahashi S, Matsumoto N, Okayama A, Suzuki N, Araki A, Okajima K, Tanaka H, Miyamoto A: FOXG1 mutations in Japanese patients with the congenital variant of Rett syndrome. Clin Genet 2011(in press)
競争的資金
  • 成長科学協会研究助成金 ラットにおける脊髄運動細胞の生後発達とその低酸素の影響 (平成7年、100万円)(主任研究者)
  • 日本学術振興会科学研究費補助金 若手研究(スタートアップ)脳形成異常の病態解明 -前脳特異的Cdk5欠損マウスをモデルとして-  (平成18年-19年 264万円)(研究代表者)
  • 母子保健協会小児医学研究助成  脳形成異常に関連したてんかんの病態解明 -前脳特異的Cdk5欠損マウスをモデルとして-      (平成18年、120万円)(研究代表者)
  • 日本学術振興会科学研究費補助金 基盤研究C(一般)発達期脳に及ぼすてんかん発作の影響―皮質形成異常を有するモデル動物を用いた研究 (平成22年 195万円、平成23年 130万円)(研究代表者) 
  • 厚生労働症科学研究費補助金(難治性疾患克服総合研究事業) Ellis-van Creveld症候群の疫学調査と治療指針作成 (平成22年、  分担研究者)
  • 厚生労働科学研究費補助金(難治性疾患克服総合研究事業)グルコーストランスポーター1欠損症症候群の実態と診断治療指針に関する研究 (平成23年、分担研究者 80万円)
一 言 治療法開発を目指した研究を行う。