役職名		小児科助教（学内講師）
所　属		小児科学講座
氏　名		高橋　悟
専門分野		神経学
出身大学（期）		旭川医科大学（12期）
出身高校		青森県立田名部高校
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、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 てんかん患者にしばしばみられる進行性の認知機能障害に対する治療標的を明らかにすることを目指し、脳形成異常を有するCdk5欠損マウスを用い、けいれん発作が発達期脳に及ぼす影響について検討している。
一　言		こどもの発達をみる神経科学者を目指す。
英文業績 （1996〜2007）		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 and Fujieda K: Matrix metalloproteinases in infants with posthemorrhagic hydrocephalus. Early Hum Dev 2007 (in press) Ohinata J, Suzuki N, Araki A, Takahashi S, Fujieda K and Tanaka H: Actigraphic assessment of sleep disorders in children with chronic fatigue syndrome. Brain Dev 2007 (in press) Takahashi S, Ohinata J, Makita Y, Suzuki N, Araki A, Sasaki A, Murono K, Tanaka H and 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 2007 (in press)
競争的資金		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） 母子保健協会小児医学研究助成（平成18年、120万円） 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-