1998 Fiscal Year Annual Research Report

遺伝的素因と環境因子の相互作用による神経細胞死

Research Project

Project/Area Number	09280103
Research Institution	Juntendo University
Principal Investigator	水野美邦順天堂大学, 医学部, 教授 (30049043)
Co-Investigator(Kenkyū-buntansha)	小澤敬也自治医科大学, 医学部, 教授 (30137707) 柳原武彦大阪大学, 医学部, 教授 (70243201) 小川紀雄岡山大学, 医学部, 教授 (90033208) 直井信応用生化学研究所, 脳科学研究部門, 部長 (50022786) 太田茂広島大学, 医学部, 教授 (60160503)
Keywords	神経細胞死 / パーキンソン病 / 家族性パーキンソン病 / 遺伝的素因 / 黒質神経毒 / 環境因子 / 遺伝子治療 / 神経栄耀因子
Research Abstract	本邦に多い常染色体性劣性遺伝の家族性パーキンソン病の原因遺伝子のポジショナルクローニングに成功し,Parkinと命名した.Parkin遺伝子は約1Mbの巨大遺伝子で,エクソンは12,cDNAは2,960bp,翻訳領域は1,395bpよりなり,N端にはユビキチンとの部分的ホモロジー,C端にはRING-finger様モチーフを有する.mRNAは広範に発現している.本症患者についての変異分析で,エクソン3から5の間の欠失が多く,mutational hot spotが存在した.今後Parkin蛋白の機能及びその欠損による黒質の選択的変性機序を解明することにより,パーキンソン病の大部分を占める弧発型パーキンソン病の解明にも重要な手がかりが得られると期待できる. 弧発型パーキンソン病の発症の遺伝的危険因子として,ミトコンドリア電子伝達系複合体lの24kDaサブユニット遺伝子多型が発症の危険因子になることを明らかにした.環境因子では内因性のN-methylsalsolinolが黒質毒性を有し,アポトーシスを誘発し,その合成酵素活性がパーキンソン病患者リンパ球で高いことを明らかにした.またパーキンソン病の黒質で8-HO-dGTPase及び8-HO-deoxyguanineが細胞質において上昇していることを明らかにした. パーキンソン病の遺伝子治療に関し,Adeno-associated virus vectorを利用し,パーキンソン病モデル動物の線条体に,チロシン水酸化酵素・芳香族アミノ酸脱炭酸酵素遺伝子を直接導入して症状を軽減することに成功した.

Research Products

(68 results)

All Other

All Publications (68 results)

[Publications] Kitada T: "Deletion mutation in a novel protein “Parkin" gene causes autosomal recessive juvenile parkinsonism(AR-JP)" Nature. 39. 605-608 (1998)
[Publications] Hattori N: "Allele in the 24-kDa subunit gene (NDUFV2) of mitochondrial complex l and susceptibility to Parkinson's disease" Genomics. 49. 52-58 (1998)
[Publications] Hattori N: "Point mutation (Thr240Arg and Gln311Stop) in the Parkin gene" Biochem Biophy Res Commun. 249. 754-758 (1998)
[Publications] Matsumine H: "Paralysis agitans of early onset with marked diurnal fluctuation of symptoms (PEDF) maps to the locus for autosomal recessive iuvenile parkinsonism (ARJP)" Neurology. 50. 1340-1345 (1998)
[Publications] Matsumine H: "A microdeletion spanning D6S305 co-segregates with autosomal recessive juvenile parkinsonism(ARJP)" Genomics. 49. 143-146 (1998)
[Publications] Moro H: "Pthologic and biochemical studies of juvenile parkinsonism linked to chromosome 6q" Neurology. 54. 890-892 (1998)
[Publications] Yamamura Y: "Clinical,pthologic and genetic studies on autosomal recessive early-onset parkinsonism with diurnal fluctuation" Parkinsonism & Relted Disord. 4. 65-72 (1998)
[Publications] Kobayashi T: "Polymorphism of the gene encoding dihydrolipoamide succinyltransferase is associated with the susceptibility to Parkinson disease: a population based study" Ann Neurol. 43. 120-123 (1998)
[Publications] Morikawa N: "Effects of various tetrahydroisoquinoline derivatives on mitochondrial respiration and the electron transfer complexes" J Neural Transm. 105. 677-688 (1998)
[Publications] Urabe T: "Colocalization of Bcl-2 and 4-hydroxynonenal modified proteins in microglial cells and neurons of rat grain following transient focal ischemia" Neurosci Lett. 247. 159-162 (1998)
[Publications] Mizuno: "Neurochemical and neurogenetic correlates of Parkinson's disease" J Neurochem. 71. 893-902 (1998)
[Publications] Mizuno: "A comprehensive study on the mechanism underlying the pathogenesis of Parkinson's disease and its treatment" Asian Med J. 41. 62-71 (1998)
[Publications] Mizuno: "Apoptosis in neurodegenerative disorders" Intern Med. 37. 192-193 (1998)
[Publications] Hattori N: "Molecular analysis of a novel ubiquitin-like protein (PARKIN) gene in Japanese families with AR-JP:evidence of homozygous deletions in the PARKIN gene in affected individuals" Ann Neurol. in press. (1999)
[Publications] Wang M: "Polymorphism in the parkin gene among sporadic Parkinson's desease" Ann Neurol. in press. (1999)
[Publications] Shimura H: "Immunohistochemical and subcellular localization of Parkin: absence of protein in AR-JP." Ann Neurol. in press. (1999)
[Publications] Kawai H: "Novel endogenous 1,2,3,4-tetrahydroisoquinoline derivatives: uptake by dopamine transporter and activity to induce parkinsonism" J Neurochem. 70. 745-751 (1998)
[Publications] Okada T: "Tetrahydropapaveroline and its derivatives inhibit dopamine uptake through dopamine transporter expressed in HEK293 cells" Neurosci Res. 30. 87-90 (1998)
[Publications] Kotake Y: "Deprenyl decreases an endogenous parkinsonism-inducing compound, 1-benzyl-1,2,3,4-tetrahydroisoquinoline in mice in vivo and in vitro studies" Brain Res. 787. 341-343 (1998)
[Publications] Matsubara K: "Sturactural significance of azaheterocyclic amines related to Parkinson's disease for dopamine transporter" Eur J Pharmacol. 348. 77-84 (1998)
[Publications] Yoshihara S: "Imvolvement of hepatic aldehyde oxidase in conversion of 1-methyl-4-phenyl-2,3-dehydro-pvridinium(MPDP+) to 1-methyl-4-phenyl-5,6-dihydro-2-pyridone" Arch Biochem Biophys. 360. 93-98 (1998)
[Publications] Naoi M: "(R)Salsolinol N-methyltransferase activity increases in Parkinsonian lymphocytes" Ann Neurol. 43. 2212-2216 (1998)
[Publications] Maruyama W,: "(-)-Deprenyl protects human dopaminergic neuroblastoma SH-SY5Y cells from apoptosis induced by peroxynitrite and nitric oxide" J Neurochem. 70. 2510-2515 (1998)
[Publications] Minami C: "Generation of reactive oxygen species accounts for cytotoxicity of an endogenous dopami-nergic neurotoxin,(R)-N-methylsalsolinol, to differentiated dopaminergic SH-SY5Y cells" J Neural Transm. 105. 397-405 (1998)
[Publications] Umeda M: "Oxidation of 1-amino-4-phenyl-1,2,3,6-tetrahydropyridine,a 1-amino analog of MPTP by type A and B monoamine oxidase" J Neural Transm. 105. 1253-1264 (1998)
[Publications] Ohkuwa T: "A novle assay for glutathione reductase activity by use of high performance liquied chromatography with electrochemical detection" J Chromatogr. 705. 23-28 (1998)
[Publications] Tanaka M,: "Mitochondrial genotype associated with longevity" Lancet. 351. 185-186 (1998)
[Publications] Gong JS: "Mitochondrial genotype frequent in centenarians predisposes resistance to adult onset diseases" J Clin Biochem Nutr. 24. 105-111 (1998)
[Publications] Zhang J: "Peroxide production and apoptosis in cultured cells carrying mtDNA mutation causing encephalomyopathy" Biochem Mol Biol Int. 46. 71-79 (1998)
[Publications] Borgeld H-JW: "Appropriately spaced nuclear localizing signals are necessary for efficient nuclear import of non-nuclear proteins" Biochem Biophys Res Commun.in press. (1999)
[Publications] Ikemoto K: "Does tyrosinase exist in the neuromelanin-pigmented neurons in the human substantia nigra?" Neurosci Lett. 253. 198-200 (1998)
[Publications] Ikemoto K: "A dopamine-synthesizing cell group demonstrated in the human basal forebrain by dual labeling immu nohistochemical technique of tyrosine hydroxylase and aromatic L-AAD" Neurosci Lett. 243. 129-132 (1998)
[Publications] Ikemoto K: "Do all of human midbrain tyrosine hydroxylase neurons synthesize dopamine?" Brain Res. 805. 255-258 (1998)
[Publications] Kitahama K: "Dopamine synthesizing enzymes in paraventricular hypothalamic neurons of the human and monkey(Macaca fuscata)" Neurosci Lett. 243. 1-4 (1998)
[Publications] Nagatsu I: "Phenylethanolamine-N-methyl-transferase- immuno reactive nerve terminals afferent to the mouse substantia nigra" Neurosci Lett. 245. 41-44 (1998)
[Publications] Nishii K: "Motor and learning dysfunctions during postnatal development in mice defective in dopamine neuronal transmission" J Neurosci Res. 54. 450-464 (1998)
[Publications] Onozuka M.: "Glial reaction linked with P-70-inuced seizure activity in the cerebral cortex of rats" Neurosci Res Commun. 23. 111-117 (1998)
[Publications] Sawada H: "Autoomic neuropathy in transgenic mice caused by immunotoxin targeting of the peripheral nervous system" J Neurosci Res. 51. 162-173 (1998)
[Publications] Fujii T: "Transient expression of only phenylethanolamine- N-methyltransferase- immunoreactive neurons in the medulla oblongata of the mouse during postnatal development" Biogenic Amines. 14(in press). (1998)
[Publications] Okuda S: "Forebrain expression of GluT3 mRNA in 6-hydroxydopamine-lesioned rats" Biogenic Amines. 14(in press). (1998)
[Publications] Kitahama K: "Aromatic L-amino acid decarboxylase and tyrosine hydroxylase immunohistochemistry in the adult human hypothalamus" J Chemical Neuroanatomy. in press. (1999)
[Publications] Nagatsu I: "Specific localization of the guanosine triphosphate (GTP)cyclohydrolase I-immunoreactivity in the human brain" J Neural Transm. in press. (1999)
[Publications] Iida K: "Effects of repeated cyclosporin A administration on immunodipropionitrile-induced dyskinesia and TRE-/CRE-binding activities in rat brain" Neurosci Res. 30. 185-193 (1998)
[Publications] Gomez-Vargas,M.,: "Pergolide scavenges both hydroxyl and nitric oxide free radicals in vitro and inhibits lipid peroxidation in different regionsof the rat brain" Brain Res. 790. 202-208 (1998)
[Publications] Kondo F: "Indomethacin inhibits delayed DNA fragmentation of hippocampal CA1 pyramidal neurons after transient forebrain ischemia in gergiles" Brain Res. 791. 352-356 (1998)
[Publications] Aoki C: "Stimulatory effects of 4-methylcatechol, dopamine and levodopa on the expresson of metallothionein-III(GIF)mRNA in immoralized mouse brain glial cells(VR-2g)" Brain Res. 792. 335-339 (1998)
[Publications] Iwata E: "Protective effects of nicergoline against hydrogenn peroxide toxicity in neuronal cell line." Neurosci Lett. 251. 49-52 (1998)
[Publications] Yokoi I: "Effects of kynurenine metabolites on the electrocorticographic activity in the rat" J Neural Tranms. 105. 147-160 (1998)
[Publications] Tanaka K: "Chronic cerebral hypoperfusion disrups discriminative behavior in acquired-learning rats" J Neurosci Methods. 84. 63-68 (1998)
[Publications] Matsushita K: "Alterations of BCL-2 family proteins precede cytoskeletal proteolysis in the penumbra,but no in infarct centres following focal cerebral ischemia in mice" Neuroscience. 83. 439-448 (1998)
[Publications] Nakano M: "Measurement of regional N-acetyl aspartate after transient globalischemia in gerbils with and without ischemic tolerance: an index of neuronal survival" Ann Neurol. 44. 334-340 (1998)
[Publications] Hata R: "Brainstem auditory evoked potentials during brainstem ischemia and reperfusion in gerbils" Neuroscience. 83. 201-213 (1998)
[Publications] Kitagawa K: "Cerebral ischemia after bilateral carotid artery occlusion and intraluminal suture occlusion in mice: evaluation of the patency of the posterior communicating artery" J Cereb Blood Flow Metab. 18. 570-579 (1998)
[Publications] Kitagawa K: "Deficiency of intercellular adhesion molecule 1 attenuates microcirculatory disturbance and infarction size in focal cerebral ischemia" Cereb Blood Flow Metab. 18. 1336-1345 (1998)
[Publications] Imuta N: "Induction of 72-KDa inducible heat shock protein 72(HSP72)in cultured rat astrocytes after energy depletion" J Neurochem. 70. 550-557 (1998)
[Publications] Ogasawara Y: "The use of heterologous promoters for adeno-associated virus (AAV) protein expression in AAV vector production" Microbiol Immunol. 42. 177-185 (1998)
[Publications] Fan D: "Behavioral recovery in 6-OHDA-lesioned rats by contransduction of striatum with tyrosine hydroxylase and aromatic L-amino acid decarboxylase genes using two separate AAV vectors" Hum Gene Ther. 9. 2527-2535 (1998)
[Publications] Fan D: "Prevention of dopaminergic neuron death by adeno-associated virus vector-mediated GDNF gene transfer in rat mesencephalic cells in vitro" Neurosci Lett. 248. 61-64 (1998)
[Publications] Maeda Y: "Efficient gene transfer into cardiac myocytes using adeno-associated virus (AAV) vectors" J Mol Cell Cardiol. 30. 1341-1348 (1998)
[Publications] Kokubun K: "Apoptosis mediated regulation of recombinant human granulocyte colony-stimulating factor production by genetically engineered fibroblast" Gene Ther. 5. 923-929 (1998)
[Publications] Shinoura N: "Construction,propagation,and titer estimation of recombinant adenoviruses carrying proapoptotic genes" Hum Gene Ther. 9. 2683-2689 (1998)
[Publications] Morikawa E: "Attenuation of focal ischemic brain injury in mice deficient in the epsilon 1 (NR2A)subunit of NMDA receptor" J Neurosci. 18. 9727-9732 (1998)
[Publications] Shinoura N: "Apoptosis by retrovirus- and adenovirus-mediated gene transfer of Fas ligand to geioma cells. implications for gene therapy" Hum Gene Ther. 9. 1983-1993 (1998)
[Publications] Kawahara N: "Propentofylline potentiates induced tolerance in gerbil hippocampal neurons via adenosine receptor" J Cereb Blood Flow Metab. 18. 472-475 (1998)
[Publications] Todo T: "Neuroant iocalization of fibroblast growth factor-9 immunoreactivity in human and rat brain." Brain Res. 783. 179-187 (1998)
[Publications] Kawai K: "Preconditioning in vivo ischemia inhibits anoxic long-term potentiation and functronally protects CA1 neurons in the gerbil" J Cereb Blood Flow Metab. 18. 288-296 (1998)
[Publications] Mizuno Y: "Mitochondrial dysfunction in Parkinson's disease" Olanow CW,Jenner P,eds,Wells Medical Limited Beyond The Decade Of The Brain,Neuroprotection in Parkinson's Disease volume 3, 189-202 (1998)
[Publications] Mizuno Y: "Genetic aspects of Parkinson's disease" Fisher A,Hanin I,Yoshida M,eds,Plenum Press Progress in Alzheimer's and Parkinson's Diseases, 393-399 (1998)

1998 Fiscal Year Annual Research Report

遺伝的素因と環境因子の相互作用による神経細胞死

Principal Investigator

水野 美邦 順天堂大学, 医学部, 教授 (30049043)

Research Products

[Publications] Kitada T: "Deletion mutation in a novel protein “Parkin" gene causes autosomal recessive juvenile parkinsonism(AR-JP)" Nature. 39. 605-608 (1998)

[Publications] Hattori N: "Allele in the 24-kDa subunit gene (NDUFV2) of mitochondrial complex l and susceptibility to Parkinson's disease" Genomics. 49. 52-58 (1998)

[Publications] Hattori N: "Point mutation (Thr240Arg and Gln311Stop) in the Parkin gene" Biochem Biophy Res Commun. 249. 754-758 (1998)

[Publications] Matsumine H: "Paralysis agitans of early onset with marked diurnal fluctuation of symptoms (PEDF) maps to the locus for autosomal recessive iuvenile parkinsonism (ARJP)" Neurology. 50. 1340-1345 (1998)

[Publications] Matsumine H: "A microdeletion spanning D6S305 co-segregates with autosomal recessive juvenile parkinsonism(ARJP)" Genomics. 49. 143-146 (1998)

[Publications] Moro H: "Pthologic and biochemical studies of juvenile parkinsonism linked to chromosome 6q" Neurology. 54. 890-892 (1998)

[Publications] Yamamura Y: "Clinical,pthologic and genetic studies on autosomal recessive early-onset parkinsonism with diurnal fluctuation" Parkinsonism & Relted Disord. 4. 65-72 (1998)

[Publications] Kobayashi T: "Polymorphism of the gene encoding dihydrolipoamide succinyltransferase is associated with the susceptibility to Parkinson disease: a population based study" Ann Neurol. 43. 120-123 (1998)

[Publications] Morikawa N: "Effects of various tetrahydroisoquinoline derivatives on mitochondrial respiration and the electron transfer complexes" J Neural Transm. 105. 677-688 (1998)

[Publications] Urabe T: "Colocalization of Bcl-2 and 4-hydroxynonenal modified proteins in microglial cells and neurons of rat grain following transient focal ischemia" Neurosci Lett. 247. 159-162 (1998)

[Publications] Mizuno: "Neurochemical and neurogenetic correlates of Parkinson's disease" J Neurochem. 71. 893-902 (1998)

[Publications] Mizuno: "A comprehensive study on the mechanism underlying the pathogenesis of Parkinson's disease and its treatment" Asian Med J. 41. 62-71 (1998)

[Publications] Mizuno: "Apoptosis in neurodegenerative disorders" Intern Med. 37. 192-193 (1998)

[Publications] Hattori N: "Molecular analysis of a novel ubiquitin-like protein (PARKIN) gene in Japanese families with AR-JP:evidence of homozygous deletions in the PARKIN gene in affected individuals" Ann Neurol. in press. (1999)

[Publications] Wang M: "Polymorphism in the parkin gene among sporadic Parkinson's desease" Ann Neurol. in press. (1999)

[Publications] Shimura H: "Immunohistochemical and subcellular localization of Parkin: absence of protein in AR-JP." Ann Neurol. in press. (1999)

[Publications] Kawai H: "Novel endogenous 1,2,3,4-tetrahydroisoquinoline derivatives: uptake by dopamine transporter and activity to induce parkinsonism" J Neurochem. 70. 745-751 (1998)

[Publications] Okada T: "Tetrahydropapaveroline and its derivatives inhibit dopamine uptake through dopamine transporter expressed in HEK293 cells" Neurosci Res. 30. 87-90 (1998)

[Publications] Kotake Y: "Deprenyl decreases an endogenous parkinsonism-inducing compound, 1-benzyl-1,2,3,4-tetrahydroisoquinoline in mice in vivo and in vitro studies" Brain Res. 787. 341-343 (1998)

[Publications] Matsubara K: "Sturactural significance of azaheterocyclic amines related to Parkinson's disease for dopamine transporter" Eur J Pharmacol. 348. 77-84 (1998)

[Publications] Yoshihara S: "Imvolvement of hepatic aldehyde oxidase in conversion of 1-methyl-4-phenyl-2,3-dehydro-pvridinium(MPDP+) to 1-methyl-4-phenyl-5,6-dihydro-2-pyridone" Arch Biochem Biophys. 360. 93-98 (1998)

[Publications] Naoi M: "(R)Salsolinol N-methyltransferase activity increases in Parkinsonian lymphocytes" Ann Neurol. 43. 2212-2216 (1998)

[Publications] Maruyama W,: "(-)-Deprenyl protects human dopaminergic neuroblastoma SH-SY5Y cells from apoptosis induced by peroxynitrite and nitric oxide" J Neurochem. 70. 2510-2515 (1998)

[Publications] Minami C: "Generation of reactive oxygen species accounts for cytotoxicity of an endogenous dopami-nergic neurotoxin,(R)-N-methylsalsolinol, to differentiated dopaminergic SH-SY5Y cells" J Neural Transm. 105. 397-405 (1998)

[Publications] Umeda M: "Oxidation of 1-amino-4-phenyl-1,2,3,6-tetrahydropyridine,a 1-amino analog of MPTP by type A and B monoamine oxidase" J Neural Transm. 105. 1253-1264 (1998)

[Publications] Ohkuwa T: "A novle assay for glutathione reductase activity by use of high performance liquied chromatography with electrochemical detection" J Chromatogr. 705. 23-28 (1998)

[Publications] Tanaka M,: "Mitochondrial genotype associated with longevity" Lancet. 351. 185-186 (1998)

[Publications] Gong JS: "Mitochondrial genotype frequent in centenarians predisposes resistance to adult onset diseases" J Clin Biochem Nutr. 24. 105-111 (1998)

[Publications] Zhang J: "Peroxide production and apoptosis in cultured cells carrying mtDNA mutation causing encephalomyopathy" Biochem Mol Biol Int. 46. 71-79 (1998)

[Publications] Borgeld H-JW: "Appropriately spaced nuclear localizing signals are necessary for efficient nuclear import of non-nuclear proteins" Biochem Biophys Res Commun.in press. (1999)

[Publications] Ikemoto K: "Does tyrosinase exist in the neuromelanin-pigmented neurons in the human substantia nigra?" Neurosci Lett. 253. 198-200 (1998)

[Publications] Ikemoto K: "A dopamine-synthesizing cell group demonstrated in the human basal forebrain by dual labeling immu nohistochemical technique of tyrosine hydroxylase and aromatic L-AAD" Neurosci Lett. 243. 129-132 (1998)

[Publications] Ikemoto K: "Do all of human midbrain tyrosine hydroxylase neurons synthesize dopamine?" Brain Res. 805. 255-258 (1998)

[Publications] Kitahama K: "Dopamine synthesizing enzymes in paraventricular hypothalamic neurons of the human and monkey(Macaca fuscata)" Neurosci Lett. 243. 1-4 (1998)

[Publications] Nagatsu I: "Phenylethanolamine-N-methyl-transferase- immuno reactive nerve terminals afferent to the mouse substantia nigra" Neurosci Lett. 245. 41-44 (1998)

[Publications] Nishii K: "Motor and learning dysfunctions during postnatal development in mice defective in dopamine neuronal transmission" J Neurosci Res. 54. 450-464 (1998)

[Publications] Onozuka M.: "Glial reaction linked with P-70-inuced seizure activity in the cerebral cortex of rats" Neurosci Res Commun. 23. 111-117 (1998)

[Publications] Sawada H: "Autoomic neuropathy in transgenic mice caused by immunotoxin targeting of the peripheral nervous system" J Neurosci Res. 51. 162-173 (1998)

[Publications] Fujii T: "Transient expression of only phenylethanolamine- N-methyltransferase- immunoreactive neurons in the medulla oblongata of the mouse during postnatal development" Biogenic Amines. 14(in press). (1998)

[Publications] Okuda S: "Forebrain expression of GluT3 mRNA in 6-hydroxydopamine-lesioned rats" Biogenic Amines. 14(in press). (1998)

[Publications] Kitahama K: "Aromatic L-amino acid decarboxylase and tyrosine hydroxylase immunohistochemistry in the adult human hypothalamus" J Chemical Neuroanatomy. in press. (1999)

[Publications] Nagatsu I: "Specific localization of the guanosine triphosphate (GTP)cyclohydrolase I-immunoreactivity in the human brain" J Neural Transm. in press. (1999)

[Publications] Iida K: "Effects of repeated cyclosporin A administration on immunodipropionitrile-induced dyskinesia and TRE-/CRE-binding activities in rat brain" Neurosci Res. 30. 185-193 (1998)

[Publications] Gomez-Vargas,M.,: "Pergolide scavenges both hydroxyl and nitric oxide free radicals in vitro and inhibits lipid peroxidation in different regionsof the rat brain" Brain Res. 790. 202-208 (1998)

[Publications] Kondo F: "Indomethacin inhibits delayed DNA fragmentation of hippocampal CA1 pyramidal neurons after transient forebrain ischemia in gergiles" Brain Res. 791. 352-356 (1998)

[Publications] Aoki C: "Stimulatory effects of 4-methylcatechol, dopamine and levodopa on the expresson of metallothionein-III(GIF)mRNA in immoralized mouse brain glial cells(VR-2g)" Brain Res. 792. 335-339 (1998)

[Publications] Iwata E: "Protective effects of nicergoline against hydrogenn peroxide toxicity in neuronal cell line." Neurosci Lett. 251. 49-52 (1998)

[Publications] Yokoi I: "Effects of kynurenine metabolites on the electrocorticographic activity in the rat" J Neural Tranms. 105. 147-160 (1998)

[Publications] Tanaka K: "Chronic cerebral hypoperfusion disrups discriminative behavior in acquired-learning rats" J Neurosci Methods. 84. 63-68 (1998)

[Publications] Matsushita K: "Alterations of BCL-2 family proteins precede cytoskeletal proteolysis in the penumbra,but no in infarct centres following focal cerebral ischemia in mice" Neuroscience. 83. 439-448 (1998)

[Publications] Nakano M: "Measurement of regional N-acetyl aspartate after transient globalischemia in gerbils with and without ischemic tolerance: an index of neuronal survival" Ann Neurol. 44. 334-340 (1998)

[Publications] Hata R: "Brainstem auditory evoked potentials during brainstem ischemia and reperfusion in gerbils" Neuroscience. 83. 201-213 (1998)

[Publications] Kitagawa K: "Cerebral ischemia after bilateral carotid artery occlusion and intraluminal suture occlusion in mice: evaluation of the patency of the posterior communicating artery" J Cereb Blood Flow Metab. 18. 570-579 (1998)

[Publications] Kitagawa K: "Deficiency of intercellular adhesion molecule 1 attenuates microcirculatory disturbance and infarction size in focal cerebral ischemia" Cereb Blood Flow Metab. 18. 1336-1345 (1998)

[Publications] Imuta N: "Induction of 72-KDa inducible heat shock protein 72(HSP72)in cultured rat astrocytes after energy depletion" J Neurochem. 70. 550-557 (1998)

[Publications] Ogasawara Y: "The use of heterologous promoters for adeno-associated virus (AAV) protein expression in AAV vector production" Microbiol Immunol. 42. 177-185 (1998)

[Publications] Fan D: "Behavioral recovery in 6-OHDA-lesioned rats by contransduction of striatum with tyrosine hydroxylase and aromatic L-amino acid decarboxylase genes using two separate AAV vectors" Hum Gene Ther. 9. 2527-2535 (1998)

[Publications] Fan D: "Prevention of dopaminergic neuron death by adeno-associated virus vector-mediated GDNF gene transfer in rat mesencephalic cells in vitro" Neurosci Lett. 248. 61-64 (1998)

[Publications] Maeda Y: "Efficient gene transfer into cardiac myocytes using adeno-associated virus (AAV) vectors" J Mol Cell Cardiol. 30. 1341-1348 (1998)

[Publications] Kokubun K: "Apoptosis mediated regulation of recombinant human granulocyte colony-stimulating factor production by genetically engineered fibroblast" Gene Ther. 5. 923-929 (1998)

[Publications] Shinoura N: "Construction,propagation,and titer estimation of recombinant adenoviruses carrying proapoptotic genes" Hum Gene Ther. 9. 2683-2689 (1998)

[Publications] Morikawa E: "Attenuation of focal ischemic brain injury in mice deficient in the epsilon 1 (NR2A)subunit of NMDA receptor" J Neurosci. 18. 9727-9732 (1998)

[Publications] Shinoura N: "Apoptosis by retrovirus- and adenovirus-mediated gene transfer of Fas ligand to geioma cells. implications for gene therapy" Hum Gene Ther. 9. 1983-1993 (1998)

[Publications] Kawahara N: "Propentofylline potentiates induced tolerance in gerbil hippocampal neurons via adenosine receptor" J Cereb Blood Flow Metab. 18. 472-475 (1998)

[Publications] Todo T: "Neuroant iocalization of fibroblast growth factor-9 immunoreactivity in human and rat brain." Brain Res. 783. 179-187 (1998)

[Publications] Kawai K: "Preconditioning in vivo ischemia inhibits anoxic long-term potentiation and functronally protects CA1 neurons in the gerbil" J Cereb Blood Flow Metab. 18. 288-296 (1998)

[Publications] Mizuno Y: "Mitochondrial dysfunction in Parkinson's disease" Olanow CW,Jenner P,eds,Wells Medical Limited Beyond The Decade Of The Brain,Neuroprotection in Parkinson's Disease volume 3, 189-202 (1998)

[Publications] Mizuno Y: "Genetic aspects of Parkinson's disease" Fisher A,Hanin I,Yoshida M,eds,Plenum Press Progress in Alzheimer's and Parkinson's Diseases, 393-399 (1998)

水野美邦順天堂大学, 医学部, 教授 (30049043)