1998 年度実績報告書

胎児・新生児脳組織バンキングによる脳障害の分子発生病理学的研究

研究課題

研究課題/領域番号	10470221
研究機関	国立精神・神経センター
研究代表者	高嶋幸男国立精神・神経センター, 疾病研究第2部, 部長 (70038743)
研究分担者	大湯淳功国立精神, 神経センター・疾病研究第2部, 研究員伊藤雅之国立精神, 神経センター・疾病研究第2部, 研究員 (50243407) 岡明国立精神, 神経センター・疾病研究第2部, 研究員 (00251273)
キーワード	脳バンク / 新生児脳障害 / 乳幼児突然死症候群 / 小児遺伝性神経疾患 / グルタミン酸受容体 / ドーパミン受容体
研究概要	1. 発達期脳組織バンキングのシステム化。承諾を得た胎児・新生児・小児の剖検に際し、脳検索例は1,200例をこし、脳および主要臓器の一部の新鮮生組織の凍結保存例は、その約4分の1と増加した。各施設の剖検例は減少しているために、本システムは長期継続したい。生化学的、分子生物学的ならびに組織化学的な協同研究への利用も増加しつつある。 2. 発達期脳の生化学的、分子生物学的ならびに免疫組織化学的研究。周産期の低酸素性虚血性脳障害の発生に関与する因子は多く、血管、フリーラジカル、グルタミン・ドーパミン酸受容体、一酸化窒素、アポトーシス関連因子を発達的免疫組織化学的にみて、周産期の脳の特徴を明らかにした。これに基づいて、低酸素性虚血性脳障害例の病変を経時的に調べ、小脳で特有のグルタミン酸トランスポータ(EAAT4,GKLST)が細胞障害の早期から作用していること、基底核壊死ではドーパミンD2受容体が神経細胞の変性と可塑性に関与していること、脳室周囲白質軟化では血管内皮成長因子が壊死巣修復に作用していることが分かった。また、乳幼児突然死症候群の脳が集積され、検索され、延髄呼吸調節中枢のカテコラミンやセロトニン神経細胞の異常が発見され、更に上位中枢の異常があることが分かった。最近、遺伝性の小児神経疾患の遺伝子が発見され、病態を分子病理学的に検討し、滑脳症(Miller-Dieker症候群など)、神経皮膚症候群(結節性硬化症、Recklinghausen病)、ataxiateleangiectasiaや皮質形成異常の特異性が明らかになってきた。このように、脳組織バンキングの資料は有効に活用されており、今後の病態研究にも活用したい。

研究成果

(25件)

すべてその他

すべて文献書誌 (25件)

[文献書誌] Obonai T,Mizuguchi M,Takashima S: "Developmental and aging changes of Bak expression in the human brain" Brain Research. 783. 167-170 (1998)
[文献書誌] Obonai T,Yasuhara Y,Nakamura T,Takashima S: "Catecholamine neurons alteration in the brainstem of sudden infant death syndrome victims" Pediatrics. 101. 285-288 (1998)
[文献書誌] Inage Y.W.,Itoh M,Wada K,Takashima S: "Expression of two glutamate transporters.GLAST and EAAT4,in the human cerebellum:their correlation in development and neonatal hypoxic-ischemic damage" J of Neuropathology and Experimental Neurology. 57. 554-562 (1998)
[文献書誌] Meng S.Z,Isumi H,Takashima S: "Neuropathological characteristics and alteration of the dopamine D_2 receptor in hypoxic-ischemic basal ganglia necrosis" Brain & Dev. 20. 98-104 (1998)
[文献書誌] Kato M,Mizuguchi M,Hattori S,Nakamura S,Takashima S: "Loss of neurofibromin in the leptomeningeal astroglial heterotopia of NF-1" Pediatr Neurol. 18. 227-230 (1998)
[文献書誌] Oka A,Takashima S: "Expression of the ataxia-telangiectasia gene(ATM)product in human cerebellar neurons during development" Neuroscience Letters. 252. 195-198 (1998)
[文献書誌] Oka A,Kurachi Y,Mizuguchi M,Hayashi M,Takashima S: "Expression of late infantile neuronal ceroid lipofuscinosis(CLN2)gene product in human brains" Neuroscience Letters. 257. 113-115 (1998)
[文献書誌] Takashima S,Mizuguchi M,Arii N: "Neuronal migration disorder:expression of gene products in the neocortex" Neuropathology. 18. 427-432 (1998)
[文献書誌] Ozawa H,Takashima S: "Immunocytochemical Devlopment of transferrin and ferritin immunoreactivity in the human pons and cerebellum" J.of Child Neurology. 13. 59-63 (1998)
[文献書誌] Obonai T,Mizuguchi M,Takashima S: "Developmental and aging changes of Bak expression in the human brain" Brain Research. 783. 167-170 (1998)
[文献書誌] Meng S.Z,Obonai T,Takashima S: "A developmental study of the dopamine D2R receptors in the human basal ganglia and thalamus" Harly Human Dev. 51. 23-30 (1998)
[文献書誌] Ohyu J,Takashima S: "Developmental characteristics of neuronal nitric oxide synthase(nNOS)immunoreactive neurons in fetal to adolescent human brains" Dev Brain Res. 110. 193-202 (1998)
[文献書誌] Miyawaki T,Matsui K,Takashima S: "Developmental characteristics of vessel density in the human fetal and infant brains" Early Human development. 53. 65-72 (1998)
[文献書誌] Obonai T,Yasuhara Y,Nakamura T,Takashima S: "Catecholamine neurons alteration in the brainstem of sudden infant death syndrome victims" Pediatrics. 101. 285-288 (1998)
[文献書誌] Obonai T,Takashima S: "In utero brain lesions in SIDS" Pediatr Neurol. 19. 23-25 (1998)
[文献書誌] Inage Y.W.,Itoh M,Wada K,Takashima S: "Expression of two glutamate transporters,GLAST and EAAT4,in the human cerebellum:their correlation in development and neonatal hypoxic-ischemic damage" J of Neuropathology and Experimental Neurology. 57. 554-562 (1998)
[文献書誌] Meng S.Z,Isumi H,Takashima S: "Neuropathological characteristics and alteration of the dopamine D_2 receptor in hypoxic-ischemic basal ganglia necrosis" Brain & Dev. 20. 98-104 (1998)
[文献書誌] Ohyu J,Takashima S: "Decreased expression of microtubule-associated protein 5(MAP5)in the molecular layer of cerebellum in preterm infants with olivocrebellar lesions" Brain & Dev. 20. 22-26 (1998)
[文献書誌] Arai Y,Deguchi K,Takashima S: "Vascular endothelial growth factor in brains with periventricular leukomalacia" Pediatric Neurology. 19. 45-49 (1998)
[文献書誌] Kato M,Mizuguchi M,Hattori S,Nakamura S,Takashima S: "Loss of neurofibromin in the leptomeningeal astroglial heterotopia of NF-1" Pediatr Neurol. 18. 227-230 (1998)
[文献書誌] Isumi H,Takashima S,Ikeda K,Mizuguchi M: "Expression of a 45K subunit of platelet-activating factor acetyl-hydrolase in the developing mouse cerebellum" Anat Embryol. 197. 415-419 (1998)
[文献書誌] Oka A,Takashima S: "Expression of the ataxia-telangiectasia gene(ATM)product in human cerebellar neurons during development" Neuroscience Letters. 252. 195-198 (1998)
[文献書誌] Oka A,Kurachi Y,Mizuguchi M,Hayashi M,Takashima S: "Expression of late infantile neuronal ceroid lipofuscinosis(CLN2)gene product in human brains" Neuroscience Letters. 256. 1-3 (1998)
[文献書誌] Takashima S,Mizuguchi M,Arii N: "Neuronal migration disorder:expression of gene products in the neocortex" Neuropathology. 18. 427-432 (1998)
[文献書誌] Yamanouchi H,Jay V,Otsubo H,Kaga M,Becker L.E.,Takashima S: "Early forms of microtubule-associated protein are strongly expressed in cortical dysplasia" Acta Neuropathol. 95. 466-470 (1998)

1998 年度 実績報告書

胎児・新生児脳組織バンキングによる脳障害の分子発生病理学的研究

研究代表者

高嶋 幸男 国立精神・神経センター, 疾病研究第2部, 部長 (70038743)

研究成果

[文献書誌] Obonai T,Mizuguchi M,Takashima S: "Developmental and aging changes of Bak expression in the human brain" Brain Research. 783. 167-170 (1998)

[文献書誌] Obonai T,Yasuhara Y,Nakamura T,Takashima S: "Catecholamine neurons alteration in the brainstem of sudden infant death syndrome victims" Pediatrics. 101. 285-288 (1998)

[文献書誌] Inage Y.W.,Itoh M,Wada K,Takashima S: "Expression of two glutamate transporters.GLAST and EAAT4,in the human cerebellum:their correlation in development and neonatal hypoxic-ischemic damage" J of Neuropathology and Experimental Neurology. 57. 554-562 (1998)

[文献書誌] Meng S.Z,Isumi H,Takashima S: "Neuropathological characteristics and alteration of the dopamine D_2 receptor in hypoxic-ischemic basal ganglia necrosis" Brain & Dev. 20. 98-104 (1998)

[文献書誌] Kato M,Mizuguchi M,Hattori S,Nakamura S,Takashima S: "Loss of neurofibromin in the leptomeningeal astroglial heterotopia of NF-1" Pediatr Neurol. 18. 227-230 (1998)

[文献書誌] Oka A,Takashima S: "Expression of the ataxia-telangiectasia gene(ATM)product in human cerebellar neurons during development" Neuroscience Letters. 252. 195-198 (1998)

[文献書誌] Oka A,Kurachi Y,Mizuguchi M,Hayashi M,Takashima S: "Expression of late infantile neuronal ceroid lipofuscinosis(CLN2)gene product in human brains" Neuroscience Letters. 257. 113-115 (1998)

[文献書誌] Takashima S,Mizuguchi M,Arii N: "Neuronal migration disorder:expression of gene products in the neocortex" Neuropathology. 18. 427-432 (1998)

[文献書誌] Ozawa H,Takashima S: "Immunocytochemical Devlopment of transferrin and ferritin immunoreactivity in the human pons and cerebellum" J.of Child Neurology. 13. 59-63 (1998)

[文献書誌] Obonai T,Mizuguchi M,Takashima S: "Developmental and aging changes of Bak expression in the human brain" Brain Research. 783. 167-170 (1998)

[文献書誌] Meng S.Z,Obonai T,Takashima S: "A developmental study of the dopamine D2R receptors in the human basal ganglia and thalamus" Harly Human Dev. 51. 23-30 (1998)

[文献書誌] Ohyu J,Takashima S: "Developmental characteristics of neuronal nitric oxide synthase(nNOS)immunoreactive neurons in fetal to adolescent human brains" Dev Brain Res. 110. 193-202 (1998)

[文献書誌] Miyawaki T,Matsui K,Takashima S: "Developmental characteristics of vessel density in the human fetal and infant brains" Early Human development. 53. 65-72 (1998)

[文献書誌] Obonai T,Yasuhara Y,Nakamura T,Takashima S: "Catecholamine neurons alteration in the brainstem of sudden infant death syndrome victims" Pediatrics. 101. 285-288 (1998)

[文献書誌] Obonai T,Takashima S: "In utero brain lesions in SIDS" Pediatr Neurol. 19. 23-25 (1998)

[文献書誌] Inage Y.W.,Itoh M,Wada K,Takashima S: "Expression of two glutamate transporters,GLAST and EAAT4,in the human cerebellum:their correlation in development and neonatal hypoxic-ischemic damage" J of Neuropathology and Experimental Neurology. 57. 554-562 (1998)

[文献書誌] Meng S.Z,Isumi H,Takashima S: "Neuropathological characteristics and alteration of the dopamine D_2 receptor in hypoxic-ischemic basal ganglia necrosis" Brain & Dev. 20. 98-104 (1998)

[文献書誌] Ohyu J,Takashima S: "Decreased expression of microtubule-associated protein 5(MAP5)in the molecular layer of cerebellum in preterm infants with olivocrebellar lesions" Brain & Dev. 20. 22-26 (1998)

[文献書誌] Arai Y,Deguchi K,Takashima S: "Vascular endothelial growth factor in brains with periventricular leukomalacia" Pediatric Neurology. 19. 45-49 (1998)

[文献書誌] Kato M,Mizuguchi M,Hattori S,Nakamura S,Takashima S: "Loss of neurofibromin in the leptomeningeal astroglial heterotopia of NF-1" Pediatr Neurol. 18. 227-230 (1998)

[文献書誌] Isumi H,Takashima S,Ikeda K,Mizuguchi M: "Expression of a 45K subunit of platelet-activating factor acetyl-hydrolase in the developing mouse cerebellum" Anat Embryol. 197. 415-419 (1998)

[文献書誌] Oka A,Takashima S: "Expression of the ataxia-telangiectasia gene(ATM)product in human cerebellar neurons during development" Neuroscience Letters. 252. 195-198 (1998)

[文献書誌] Oka A,Kurachi Y,Mizuguchi M,Hayashi M,Takashima S: "Expression of late infantile neuronal ceroid lipofuscinosis(CLN2)gene product in human brains" Neuroscience Letters. 256. 1-3 (1998)

[文献書誌] Takashima S,Mizuguchi M,Arii N: "Neuronal migration disorder:expression of gene products in the neocortex" Neuropathology. 18. 427-432 (1998)

[文献書誌] Yamanouchi H,Jay V,Otsubo H,Kaga M,Becker L.E.,Takashima S: "Early forms of microtubule-associated protein are strongly expressed in cortical dysplasia" Acta Neuropathol. 95. 466-470 (1998)

1998 年度実績報告書

高嶋幸男国立精神・神経センター, 疾病研究第2部, 部長 (70038743)