1997 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 Category	Grant-in-Aid for Scientific Research on Priority Areas
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) 永津郁子藤田保健衛生大学, 医学部, 教授 (80084573) 直井信名古屋工業大学, 工学部, 教授 (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	遺伝的素因と環境因子の相互作用により発症する代表的疾患であるパーキンソン病の発症機序に関し,大きな進歩があった.遺伝的素因では,Mn SOD,αケトグルタル酸脱水素酵素複合体のE2component,ミトコンドリア電子伝達複合体lの24Kサブユニット,カテコールOメチル転移酵素各遺伝子の遺伝子型がパーキンソン病発症の危険因子となることを明らかにした.更に本邦に比較的多い常染色体性劣性遺伝を示し,レビー小体の出現しない若年性パーキンソニズムの大部分が6番染色体長腕に連鎖し,遺伝学的に同一の疾患であることを明らかにした.本症の原因遺伝子クローニングも間近にせまり,黒質の選択的変性機序解明に向かい前進ができた. 環境因子あるいは内因性・外因性黒質毒性物質に関しては,ドーパミンから生成する内因性テトラハイドロイソキノリン化合物の一種であるN-methyl-(R)salsolinolが黒質に対して強力な毒性を有し,アポトーシスを誘導することを明らかにした.更にパーキンソン病患者には,本物質を合成する中性Nメチル転移酵素活性が高い一群があることを明らかにした. パーキンソン病の将来の遺伝子治療にむけ,adeno-associated virus vector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組み込み,ラットの実験的パーキンソニズムに対し,著明な症状の改善が得られることを明らかにした.また,GDNF遺伝子を培養黒質細胞にtransfectすることにより,細胞の寿命を延長できることを明らかにした.これらは,近い将来ヒトパーキンソン病の治療に応用可能であると考えられる.

Research Products

(67 results)

All Other

All Publications (67 results)

[Publications] Matsumine H, Shimizu Y, Kobayashi T, Mizuno Y,et al.: "Paralysis agitans of early onset with marked diurnal fluctuation of symptoms (PEDF) maps to the locus for autosomal recessive juvenile parkinsonism (ARJP)" Neurology. (in ptess). (1998)
[Publications] Hattori N, Yoshino H, Tanaka M, Suzuki H, Mizuno Y: "Allele in the 24-kDa subunit gene (NDUFV2) of mitochondrial complex 1 and susceptibility to Parkinson′s disease" Genomics. (in press). (1998)
[Publications] Kobayashi T, Matsumine H, Matuda S, Mizuno Y,et al.: "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] Koshimura I, lmai H, Hidano T, Endo K, Mizuno Y,et al.: "Dimethoxyphenylethylamine and tetrahydropapaverine are toxic to nigrostriatal system" Brain Res. (in press). (1998)
[Publications] Morikawa N, Naoi M, Maruyama W, Ohta S, Kotake Y, Mizuno Y,et al.: "Effects of various tetrahydroisoquinoline derivatives on mitochonrial respiration and the electron transfer complexes" J Neural Transm. (in press). (1998)
[Publications] Matsumine H, Saito M, Shimoda-Matsubayashi S, Mizuno Y,et al.: "Localization of a gene for an autosomal recessive form of juvenile parkinsonism to chromosome 6q25.2-27" Am J Hum Genet. 60. 588-596 (1997)
[Publications] Mishima K, Asai A, Kodamatsu K, Ino Y, Kirino T,et al.: "lncreased expression of midkine during the progression of human astrocytomas" Neurosci Lett. 233. 29-32 (1997)
[Publications] Ogasawara Y, Urabe M, Ozawa K: "The use of heterologous promotoers for adeno-associated virus (AAV) protein expression in AAV vector production" Mlcrobiol lmmunol. (in press). (1998)
[Publications] Surosky RT, Urabe M, Ozawa K,et al.: "Adeno-associated virus Rep proteins target DNA sequences to a unique locus in the human genome" J Virol. 71. 7951-7959 (1997)
[Publications] Surosky RT, Urabe M, Ozawa K,et al.: "Adeno-associated virus Rep proteins target DNA sequences to a unique locus in the human genome" J Virol. 71. 7951-7959 (1997)Urabe M, Hasumi Y, Ozawa K,et al.:
[Publications] "A novel dicistronic AAV (adeno-associated virus) vector using a short lRES (internal ribosome entry site) segment derived from hepatitis C virus genome" Gene. 200. 157-162 (1997)
[Publications] Maeda Y, Ikada U, Ozawa K,et al.: "Gene transfer into vascular cells using adeno-associated virus (AAV) vectors" Cardiovascular Res. 35. 514-521 (1997)
[Publications] Kawai H, Makino Y, Hirobe M, Ohta S,et al.: "Novel endogenous1,2,3,4-tetrahydroisoquinoline derivatives : uptake by dopamine transporter and activity to induce parkinsonism" J Neurochem. (in press). (1998)
[Publications] Kotake Y, Tasaki Y, Hirobe M, Ohta S,et al.: "Deprenyl decreases an endogenous parkinsonism-inducing compound,1-benzyl-1,2,3,4-tetrahydroisoquinoline in mice : in vivo and vitro studies" Brain Res. (in press). (1998)
[Publications] Okada T, Sato K, Shimada S, Ohta S,et al.: "Tetrahydropapaveroline and its derivatives inhibit dopamine uptake through dopamine trnsporter expressed in HEK293 cells" Brain Res. (in press ). (1998)
[Publications] Takahashi T, Maruyama W, Deng Y, Ohta S,et al.: "Cytotoxicity of endogenous isoquinolines to human dopaminergic neuroblastoma SH-SY5Y cells" J Neural Transm. 104. 59-66 (1997)
[Publications] Yamakawa T, Ohta S: "lsolation of 1-methyl-1,2,3,4-tetrahydroisoquinoline-synthesizing enzyme from rat brain : a possible Parkinson's disease-preventing enzyme" Biochem Biophys Res Commun. 236. 676-681 (1997)
[Publications] Naoi M, Maruyama W, Nakao N,et al.: "(R) Salsolionl N-methyltransferase activity increses in parkinsonian lymphocytes" Ann Neurol. (in press). (1998)
[Publications] Naoi M, Maruyama W, Matsubara K,et al.: "A neutral N-methyltransferase activity in the striatum determines the level of an endogenous MPP^+-like neurotoxin,1,2-dimethyl-6,7-dihydroxyisoquinoln ium ion,in the subustantia nigra" Neurosci Lett. 235. 81-81 (1997)
[Publications] Maruyama W, Strolin Benedetti M, Takahashi T,et al.: "A neurotoxin N-methy (R) salsolinol induces apoptotic cell death in differentiated human dopaminergic neuroblastoma SH-SY5Y cells" Neurocsi Lett. 232. 147-150 (1997)
[Publications] Maruyama W, Naoi M, Kasamatsu K,et al.: "An endogenous dopaminergic neurotoxin,N-methyl-(R)-salsolinol,induces DNA damage in human dopaminergic neuroblastoma SH-SY5Y cells" J Neurochem. 69. 322-329 (1997)
[Publications] Naruyama W, Sobue G, Matsubara K,et al.: "A dopaminergic neurotoxin,1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisquinoline,N-methyl (R) salsolinol, and its oxidation product accmulate in the nigio-striatal system" Neurosci Lett. 223. 61-64 (19997)
[Publications] Tanaka M, Gong J-S, Zhang J,et al.: "Mitochondrial genotype associated with longevity" Lancet. 351(in press). (1998)
[Publications] Islam MM, Suzuki H, Yoneda M, Tanaka M,et al.: "Primary structure of the smallest (6.4-kDa) subunit of human and bovine ubiquinol-cytochrome c reductase deduced from cDNA sequences" Biochem Mol Biol lnt. 41. 1109-1119 (1997)
[Publications] Shimoda-Matsubayashi S, Hattori T, Matsumine H, Mizuno Y,et al.: "Mn SOD activity and protein in a patient with chromosome 6-linked automal recessive parkinsonism in comparison with Prakinson's disease and control" Neurology. 49. 1257-1262 (1997)
[Publications] Yoritaka A, Hattori N, Mori H, Kato K, Mizuno Y.: "An immunohistochemical study on manganese superoxide dismutase in Parkinson's disease" J Neurol Sci. 148. 1811-186 (1997)
[Publications] Yoritaka A, Hattori N, Mori H, Kato K, Mizuno Y.: "An immunohistochemical study on manganese superoxide dismutase in Parkinson's disease" J Neurol Sci. 148. 181-186 (1997)
[Publications] Goto K, Mochizuki H, Hattori T, Nakamura N, Mizuno Y: "Neurotoxic effects of papaverine,tetrahydropapaverine and dimethoxphenylamine on dopamiergic neurons in ventral mesencephalic-striatal co-cuture" Brain Res. 754. 260-268 (1997)
[Publications] Yoshino H, Hattori N, Urabe T, Uchida K, Tanaka M, Mizuno Y: "Postichemic accumulation of lipid peroxidation products in the rat brain : immunohistochemical detection of 4-hydroxy-2-nonenal modified proteins" Brain Res. 767. 81-86 (1997)
[Publications] Mochizuki H, Mori H, Mizuno Y: "Apoptosis in neurodegenerative disorders" J Neural Transm. [Suppl]50. 125-140 (1997)
[Publications] Matsumine H, Shimizu Y, Kobayashi T, Mizuno Y,et al.: "Paralysis agitans of early onset with marked diurnal fluctuation of symptoms (PEDFR) maps to the locus for autosomal recessive juvenile parkinsonism (ARJP)" Neurology. (in press). (1998)
[Publications] Hattori N, Yoshino H, Tanaka M, Suzuki H, Mizuno Y: "Allele in the 24-kDa subunit gene(NDUFV2) of mitochondrial complex l and suscepyibility to Parknson's disease" Genomics. (in perss). (1998)
[Publications] Kobayashi T, Matsumine H, Matuda S, Mizuno Y,et al.: "Polymorphism of the gene encoding dihydrolipoamide succintlyransferase is associated with the susceptibility to Parkinson disease : a population based study" Ann Neurol. 43. 120-123 (1998)
[Publications] Koshimura I, Imai H, Hidano T, Enndo K, Mizuno Y,et al.: "Dimethoxyphenylethylamine and tetrahydropapaverine are toxic to the nigrostriatal system" Brain Res. (in perss). (1998)
[Publications] Morikawa N, Naoi M, Maruyama W, Ohta S, Kotake Y, Mizuno Y,et al.: "Effects of various tetrahydroisoquinoline derivatives on mitochondrial respiration and the electron transfer complexes" J Neural Transm. (in press). (1998)
[Publications] Matsumine H, Saito M, Shimoda-Matsubayashi S, Mizuno Y,et al.: "Localization of a gene for an autosomal recessive from of juvenile parkinsonism to chromosome 6q25.2-27" Am J Hum Genet. 60. 588-596 (1997)
[Publications] Kitagawa K, Matsumoto M, Yanagihara T,et al.: "Ischemic tolerance in hippocampal CA1 neurons studied using contralateral controls" Neuroscience. 81. 989-998 (1997)
[Publications] Yang G, Yanagihara T, Matsumoto M,et al.: "C57BL/6 strain is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains" Brain Res. 752. 209-218 (1997)
[Publications] LiLY, Ueda H, Yanagihara T,et al.: "A near-infrared spectroscopic study of cerebral ischemia and ischemic tolerance in gerbils" stroke. 28. 1451-1457 (1997)
[Publications] Mandai K, Matsumoto M, Yanagihara T,et al.: "Ischemic damage and ssubsequent proliferation of oligodendrocytes in focal cerebral ischemia" Neuroscience. 77. 849-861 (1997)
[Publications] Kawahara N, Ide T, Saito N, Kawai K, Kirino T: "Propentofyline potentiates induced tolerance in gerbil hippocampal neurons via adenosine receptor" J Cereb Blood Flow Metab. (in press). (1998)
[Publications] Nakagomi T, Kanemitsu H, Takagi K, Morikawa E, Kirino T, Tamura A: "Effect of L-arginine and NG-nitro-L-arginine on detayed neuronal death in the gerbil hippocampus" Neurol Res. 19. 426-430 (1997)
[Publications] Iida K, Iwata E, Asanuma M, Ogawa N,et al.: "Effects of repeated cyclosporin A administration on iminodipropionitrile-induced dyskinesia and TRE-/CRE-binding activities in rat brain" Neurosci Res. (in press). (1998)
[Publications] Iwata E, Asanuma M, Nishibayashi S, Ogawa N,et al.: "Differential effects of oxidative stress on activation of transcription factors in neuronal and glial cells" Mol Brain Res. 50. 213-220 (1997)
[Publications] Matsuura K, Makino H, Ogawa N: "Cyclosporin a attenuates the decrease in tyrosine hydroxylase immunoreactivity in nigrostriatal dopaminergic neurons in rats with intrastriatal injection of 6-hydroxydopamine" Exp Neurol. 146. 526-535 (1997)
[Publications] Kondo Y, Asanuma M, Nishibayashi S, Ogawa N,et al.: "Late-onset lipid peroxdation and neuronal cell death following transient forebrain ischemia in rat brain" Brain Res. 772. 37-44 (1997)
[Publications] Asanuma M, Asanuma SN,Gomez-Vargas M, Ogawa N,et al.: "Ketoprofen,a non-steroidal anti-inflammatory drug prevents the late-onset reduction of muscarinic acetylcholine receptors in the gerbil hippocampus after transient ischemia" Neurosci Lett. 225. 109-112 (1997)
[Publications] Kitagawa K, Matsumoto M, Yanagihara T,et al: "Cerebral ischemia following bilateral carotid occlusion and intraluminal suture occlusion in mice : evaluation of the patency of the posterior communicating artery" J Cereb Blood Flow Metab. (in press). (1998)
[Publications] Morikawa S, Kurauchi O, Tanaka M,et al.: "Increased mitochondrial damage by lipid peroxidation in trophoblast cells of preeclamtic placentas" Biochem Mol Biol Int. 41. 767-775 (1997)
[Publications] Nagatsu I, Sakai M, Nagatsu T.et al.: "Immunocytochemical evidence of novel catecholamine or blopterin-related neurons of mammalian brains" Adv Pharmacol. 42. 859-862 (1998)
[Publications] Ikemoto K, Kitahama k, Nagatsu I,et al.: "Demonstration of L-dopa decarboxylating neurons specific to human striatum" Neurosci Lett. 232. 111-114 (1997)
[Publications] Nagatsu I, Yamada K, Nagatsu T,et al.: "Tyrosine hydroxylase (TH)-only-immunoreactive non-catecholamiergic neurons in the brain of wild mice or the human TH transgenic do not contain GTP cyclohydrolase I" Neurosci Lett. 228. 55-57 (1997)
[Publications] Nagatsu I, Arai R, Nagatsu T,et al.: "Immunohistochemical colocalization of GTP cyclohydrolase I in the nigrostriatal system with tyrosine hydroxylase" Neurosci Lett. 224. 185-188 (1997)
[Publications] Karasawa N, Isomura G, Nagatsu I,et al.: "Coexistense of tyrosine hydroxylase and serotonin in the raphe nucleus of the laboratory shrew (Suncus murinus) during postnatal life" Dev Brain Res. 99. 121-125 (1997)
[Publications] Iida K, Iwata E, Asanuma M, Ogawa N,et al.: "Effects of repeated cyclosprin A administration on iminodipropionitrile-induced dyskinesia and TRE-/CRE-binding activities in rat brain" Neurosci Res. (in press). (1998)
[Publications] Iwata E, Asanuma M, Nishibayashi S, Ogawa N,et al.: "Differential effects of oxdative stress on activation of transcription factors in neuronal and glial cells" Mol Brain Res. 50. 213-220 (1997)
[Publications] Matsuura K, Makino H, Ogawa N: "Cyclosporin A attenuates the decrease in tyrosine hydroxylase immunoreactivity in nigrostriatal dopaminergic neurons in rats with intrastriatal injection of 6-hydroxydopamine" Exp Neurol. 146. 526-535 (1997)
[Publications] Kondo Y, Asanuma M, Nishibayashi S, Ogawa N,et al.: "Late-onset lipid peroxidation and neuronal cell death following transient forebrain ischemia in rat brain" Brain Res. 772. 37-44 (1997)
[Publications] Asanuma M, Asanuma SN, Gomez-Vargas M, Ogawa N,et al.: "Ketoprofen,a non-steroidal anti-inflammatory drug prevents the late-onset reduction of muscarinic acetylcholine receptors in the gerbil hippocampus after transient ischemia" Neurosci Lett. 225. 109-112 (1997)
[Publications] Kitagawa K, Matsumoto M, Yanagihara T,et al: "Cerebral ischemia following bilateral carotid occlusion and intraluminal suture occlusion in mice : evaluation of the patency of the posterior communicating artery" J Cereb Blood Flow Metab. (in press). (1998)
[Publications] Mizuno Y, Ikebe S, Hattori N, Mochizuki Y, Hattori Y, Kondo T: "Movement Disorders.Neurologic principles and practice (Etiology of Parkinson's disease)" Watts RL,Koller WC,eds,The McGraw-Hill,New York, 161-182(21) (1997)
[Publications] 水野美邦, 池邊紳一郎: "ミトコンドリア病(Parkinson病と老化)" 埜中征哉, 後藤雄一編,医学書院,東京, 167-182(15) (1997)
[Publications] 小笠原洋治, 小澤敬也: "医学とサイエンスシリーズ(アデノ随伴ウイルス(AAV)ベクター)" 小澤敬也編,羊土社,東京, 66-71(6) (1997)
[Publications] Naoi M, Maruyama W, Dostert P: "Handbook of Endogenous Neurotoxins (An animal model of Parkinson's disease prepared by endogenous N-methyl (R) saloolinol)" Moser A,ed,Birkhauser,Boston, 41-61(21) (1997)
[Publications] Mizuno Y, Ikebe S, Hattori N, Mochizuki H, Hattori Y, Kondo T: "Movemet Disorders. Neurologic principles and practice (Etioloy of Parkinson's disease)" Watts RL,Koller WC,eds,The McGraw-Hill,New York, 161-182(21) (1997)
[Publications] 水野美邦, 池邊紳一郎: "ミトコンドリア病(Parkinson病と老化)" 埜中征哉, 後藤雄一編,医学書院,東京, 167-182(15) (1997)
[Publications] Kirino T: "Primer on Cerebrovascular Diseases (Ischemic tolerance in Welch KMA)" Caplan LR,Reis DJ,Siesjo BK,Welr B (Eds),Academic Press,San Diego, 240-243(4) (1997)

1997 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] Matsumine H, Shimizu Y, Kobayashi T, Mizuno Y,et al.: "Paralysis agitans of early onset with marked diurnal fluctuation of symptoms (PEDF) maps to the locus for autosomal recessive juvenile parkinsonism (ARJP)" Neurology. (in ptess). (1998)

[Publications] Hattori N, Yoshino H, Tanaka M, Suzuki H, Mizuno Y: "Allele in the 24-kDa subunit gene (NDUFV2) of mitochondrial complex 1 and susceptibility to Parkinson′s disease" Genomics. (in press). (1998)

[Publications] Kobayashi T, Matsumine H, Matuda S, Mizuno Y,et al.: "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] Koshimura I, lmai H, Hidano T, Endo K, Mizuno Y,et al.: "Dimethoxyphenylethylamine and tetrahydropapaverine are toxic to nigrostriatal system" Brain Res. (in press). (1998)

[Publications] Morikawa N, Naoi M, Maruyama W, Ohta S, Kotake Y, Mizuno Y,et al.: "Effects of various tetrahydroisoquinoline derivatives on mitochonrial respiration and the electron transfer complexes" J Neural Transm. (in press). (1998)

[Publications] Matsumine H, Saito M, Shimoda-Matsubayashi S, Mizuno Y,et al.: "Localization of a gene for an autosomal recessive form of juvenile parkinsonism to chromosome 6q25.2-27" Am J Hum Genet. 60. 588-596 (1997)

[Publications] Mishima K, Asai A, Kodamatsu K, Ino Y, Kirino T,et al.: "lncreased expression of midkine during the progression of human astrocytomas" Neurosci Lett. 233. 29-32 (1997)

[Publications] Ogasawara Y, Urabe M, Ozawa K: "The use of heterologous promotoers for adeno-associated virus (AAV) protein expression in AAV vector production" Mlcrobiol lmmunol. (in press). (1998)

[Publications] Surosky RT, Urabe M, Ozawa K,et al.: "Adeno-associated virus Rep proteins target DNA sequences to a unique locus in the human genome" J Virol. 71. 7951-7959 (1997)

[Publications] Surosky RT, Urabe M, Ozawa K,et al.: "Adeno-associated virus Rep proteins target DNA sequences to a unique locus in the human genome" J Virol. 71. 7951-7959 (1997)Urabe M, Hasumi Y, Ozawa K,et al.:

[Publications] "A novel dicistronic AAV (adeno-associated virus) vector using a short lRES (internal ribosome entry site) segment derived from hepatitis C virus genome" Gene. 200. 157-162 (1997)

[Publications] Maeda Y, Ikada U, Ozawa K,et al.: "Gene transfer into vascular cells using adeno-associated virus (AAV) vectors" Cardiovascular Res. 35. 514-521 (1997)

[Publications] Kawai H, Makino Y, Hirobe M, Ohta S,et al.: "Novel endogenous1,2,3,4-tetrahydroisoquinoline derivatives : uptake by dopamine transporter and activity to induce parkinsonism" J Neurochem. (in press). (1998)

[Publications] Kotake Y, Tasaki Y, Hirobe M, Ohta S,et al.: "Deprenyl decreases an endogenous parkinsonism-inducing compound,1-benzyl-1,2,3,4-tetrahydroisoquinoline in mice : in vivo and vitro studies" Brain Res. (in press). (1998)

[Publications] Okada T, Sato K, Shimada S, Ohta S,et al.: "Tetrahydropapaveroline and its derivatives inhibit dopamine uptake through dopamine trnsporter expressed in HEK293 cells" Brain Res. (in press ). (1998)

[Publications] Takahashi T, Maruyama W, Deng Y, Ohta S,et al.: "Cytotoxicity of endogenous isoquinolines to human dopaminergic neuroblastoma SH-SY5Y cells" J Neural Transm. 104. 59-66 (1997)

[Publications] Yamakawa T, Ohta S: "lsolation of 1-methyl-1,2,3,4-tetrahydroisoquinoline-synthesizing enzyme from rat brain : a possible Parkinson's disease-preventing enzyme" Biochem Biophys Res Commun. 236. 676-681 (1997)

[Publications] Naoi M, Maruyama W, Nakao N,et al.: "(R) Salsolionl N-methyltransferase activity increses in parkinsonian lymphocytes" Ann Neurol. (in press). (1998)

[Publications] Naoi M, Maruyama W, Matsubara K,et al.: "A neutral N-methyltransferase activity in the striatum determines the level of an endogenous MPP^+-like neurotoxin,1,2-dimethyl-6,7-dihydroxyisoquinoln ium ion,in the subustantia nigra" Neurosci Lett. 235. 81-81 (1997)

[Publications] Maruyama W, Strolin Benedetti M, Takahashi T,et al.: "A neurotoxin N-methy (R) salsolinol induces apoptotic cell death in differentiated human dopaminergic neuroblastoma SH-SY5Y cells" Neurocsi Lett. 232. 147-150 (1997)

[Publications] Maruyama W, Naoi M, Kasamatsu K,et al.: "An endogenous dopaminergic neurotoxin,N-methyl-(R)-salsolinol,induces DNA damage in human dopaminergic neuroblastoma SH-SY5Y cells" J Neurochem. 69. 322-329 (1997)

[Publications] Naruyama W, Sobue G, Matsubara K,et al.: "A dopaminergic neurotoxin,1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisquinoline,N-methyl (R) salsolinol, and its oxidation product accmulate in the nigio-striatal system" Neurosci Lett. 223. 61-64 (19997)

[Publications] Tanaka M, Gong J-S, Zhang J,et al.: "Mitochondrial genotype associated with longevity" Lancet. 351(in press). (1998)

[Publications] Islam MM, Suzuki H, Yoneda M, Tanaka M,et al.: "Primary structure of the smallest (6.4-kDa) subunit of human and bovine ubiquinol-cytochrome c reductase deduced from cDNA sequences" Biochem Mol Biol lnt. 41. 1109-1119 (1997)

[Publications] Shimoda-Matsubayashi S, Hattori T, Matsumine H, Mizuno Y,et al.: "Mn SOD activity and protein in a patient with chromosome 6-linked automal recessive parkinsonism in comparison with Prakinson's disease and control" Neurology. 49. 1257-1262 (1997)

[Publications] Yoritaka A, Hattori N, Mori H, Kato K, Mizuno Y.: "An immunohistochemical study on manganese superoxide dismutase in Parkinson's disease" J Neurol Sci. 148. 1811-186 (1997)

[Publications] Yoritaka A, Hattori N, Mori H, Kato K, Mizuno Y.: "An immunohistochemical study on manganese superoxide dismutase in Parkinson's disease" J Neurol Sci. 148. 181-186 (1997)

[Publications] Goto K, Mochizuki H, Hattori T, Nakamura N, Mizuno Y: "Neurotoxic effects of papaverine,tetrahydropapaverine and dimethoxphenylamine on dopamiergic neurons in ventral mesencephalic-striatal co-cuture" Brain Res. 754. 260-268 (1997)

[Publications] Yoshino H, Hattori N, Urabe T, Uchida K, Tanaka M, Mizuno Y: "Postichemic accumulation of lipid peroxidation products in the rat brain : immunohistochemical detection of 4-hydroxy-2-nonenal modified proteins" Brain Res. 767. 81-86 (1997)

[Publications] Mochizuki H, Mori H, Mizuno Y: "Apoptosis in neurodegenerative disorders" J Neural Transm. [Suppl]50. 125-140 (1997)

[Publications] Matsumine H, Shimizu Y, Kobayashi T, Mizuno Y,et al.: "Paralysis agitans of early onset with marked diurnal fluctuation of symptoms (PEDFR) maps to the locus for autosomal recessive juvenile parkinsonism (ARJP)" Neurology. (in press). (1998)

[Publications] Hattori N, Yoshino H, Tanaka M, Suzuki H, Mizuno Y: "Allele in the 24-kDa subunit gene(NDUFV2) of mitochondrial complex l and suscepyibility to Parknson's disease" Genomics. (in perss). (1998)

[Publications] Kobayashi T, Matsumine H, Matuda S, Mizuno Y,et al.: "Polymorphism of the gene encoding dihydrolipoamide succintlyransferase is associated with the susceptibility to Parkinson disease : a population based study" Ann Neurol. 43. 120-123 (1998)

[Publications] Koshimura I, Imai H, Hidano T, Enndo K, Mizuno Y,et al.: "Dimethoxyphenylethylamine and tetrahydropapaverine are toxic to the nigrostriatal system" Brain Res. (in perss). (1998)

[Publications] Morikawa N, Naoi M, Maruyama W, Ohta S, Kotake Y, Mizuno Y,et al.: "Effects of various tetrahydroisoquinoline derivatives on mitochondrial respiration and the electron transfer complexes" J Neural Transm. (in press). (1998)

[Publications] Matsumine H, Saito M, Shimoda-Matsubayashi S, Mizuno Y,et al.: "Localization of a gene for an autosomal recessive from of juvenile parkinsonism to chromosome 6q25.2-27" Am J Hum Genet. 60. 588-596 (1997)

[Publications] Kitagawa K, Matsumoto M, Yanagihara T,et al.: "Ischemic tolerance in hippocampal CA1 neurons studied using contralateral controls" Neuroscience. 81. 989-998 (1997)

[Publications] Yang G, Yanagihara T, Matsumoto M,et al.: "C57BL/6 strain is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains" Brain Res. 752. 209-218 (1997)

[Publications] LiLY, Ueda H, Yanagihara T,et al.: "A near-infrared spectroscopic study of cerebral ischemia and ischemic tolerance in gerbils" stroke. 28. 1451-1457 (1997)

[Publications] Mandai K, Matsumoto M, Yanagihara T,et al.: "Ischemic damage and ssubsequent proliferation of oligodendrocytes in focal cerebral ischemia" Neuroscience. 77. 849-861 (1997)

[Publications] Kawahara N, Ide T, Saito N, Kawai K, Kirino T: "Propentofyline potentiates induced tolerance in gerbil hippocampal neurons via adenosine receptor" J Cereb Blood Flow Metab. (in press). (1998)

[Publications] Nakagomi T, Kanemitsu H, Takagi K, Morikawa E, Kirino T, Tamura A: "Effect of L-arginine and NG-nitro-L-arginine on detayed neuronal death in the gerbil hippocampus" Neurol Res. 19. 426-430 (1997)

[Publications] Iida K, Iwata E, Asanuma M, Ogawa N,et al.: "Effects of repeated cyclosporin A administration on iminodipropionitrile-induced dyskinesia and TRE-/CRE-binding activities in rat brain" Neurosci Res. (in press). (1998)

[Publications] Iwata E, Asanuma M, Nishibayashi S, Ogawa N,et al.: "Differential effects of oxidative stress on activation of transcription factors in neuronal and glial cells" Mol Brain Res. 50. 213-220 (1997)

[Publications] Matsuura K, Makino H, Ogawa N: "Cyclosporin a attenuates the decrease in tyrosine hydroxylase immunoreactivity in nigrostriatal dopaminergic neurons in rats with intrastriatal injection of 6-hydroxydopamine" Exp Neurol. 146. 526-535 (1997)

[Publications] Kondo Y, Asanuma M, Nishibayashi S, Ogawa N,et al.: "Late-onset lipid peroxdation and neuronal cell death following transient forebrain ischemia in rat brain" Brain Res. 772. 37-44 (1997)

[Publications] Asanuma M, Asanuma SN,Gomez-Vargas M, Ogawa N,et al.: "Ketoprofen,a non-steroidal anti-inflammatory drug prevents the late-onset reduction of muscarinic acetylcholine receptors in the gerbil hippocampus after transient ischemia" Neurosci Lett. 225. 109-112 (1997)

[Publications] Kitagawa K, Matsumoto M, Yanagihara T,et al: "Cerebral ischemia following bilateral carotid occlusion and intraluminal suture occlusion in mice : evaluation of the patency of the posterior communicating artery" J Cereb Blood Flow Metab. (in press). (1998)

[Publications] Morikawa S, Kurauchi O, Tanaka M,et al.: "Increased mitochondrial damage by lipid peroxidation in trophoblast cells of preeclamtic placentas" Biochem Mol Biol Int. 41. 767-775 (1997)

[Publications] Nagatsu I, Sakai M, Nagatsu T.et al.: "Immunocytochemical evidence of novel catecholamine or blopterin-related neurons of mammalian brains" Adv Pharmacol. 42. 859-862 (1998)

[Publications] Ikemoto K, Kitahama k, Nagatsu I,et al.: "Demonstration of L-dopa decarboxylating neurons specific to human striatum" Neurosci Lett. 232. 111-114 (1997)

[Publications] Nagatsu I, Yamada K, Nagatsu T,et al.: "Tyrosine hydroxylase (TH)-only-immunoreactive non-catecholamiergic neurons in the brain of wild mice or the human TH transgenic do not contain GTP cyclohydrolase I" Neurosci Lett. 228. 55-57 (1997)

[Publications] Nagatsu I, Arai R, Nagatsu T,et al.: "Immunohistochemical colocalization of GTP cyclohydrolase I in the nigrostriatal system with tyrosine hydroxylase" Neurosci Lett. 224. 185-188 (1997)

[Publications] Karasawa N, Isomura G, Nagatsu I,et al.: "Coexistense of tyrosine hydroxylase and serotonin in the raphe nucleus of the laboratory shrew (Suncus murinus) during postnatal life" Dev Brain Res. 99. 121-125 (1997)

[Publications] Iida K, Iwata E, Asanuma M, Ogawa N,et al.: "Effects of repeated cyclosprin A administration on iminodipropionitrile-induced dyskinesia and TRE-/CRE-binding activities in rat brain" Neurosci Res. (in press). (1998)

[Publications] Iwata E, Asanuma M, Nishibayashi S, Ogawa N,et al.: "Differential effects of oxdative stress on activation of transcription factors in neuronal and glial cells" Mol Brain Res. 50. 213-220 (1997)

[Publications] Matsuura K, Makino H, Ogawa N: "Cyclosporin A attenuates the decrease in tyrosine hydroxylase immunoreactivity in nigrostriatal dopaminergic neurons in rats with intrastriatal injection of 6-hydroxydopamine" Exp Neurol. 146. 526-535 (1997)

[Publications] Kondo Y, Asanuma M, Nishibayashi S, Ogawa N,et al.: "Late-onset lipid peroxidation and neuronal cell death following transient forebrain ischemia in rat brain" Brain Res. 772. 37-44 (1997)

[Publications] Asanuma M, Asanuma SN, Gomez-Vargas M, Ogawa N,et al.: "Ketoprofen,a non-steroidal anti-inflammatory drug prevents the late-onset reduction of muscarinic acetylcholine receptors in the gerbil hippocampus after transient ischemia" Neurosci Lett. 225. 109-112 (1997)

[Publications] Kitagawa K, Matsumoto M, Yanagihara T,et al: "Cerebral ischemia following bilateral carotid occlusion and intraluminal suture occlusion in mice : evaluation of the patency of the posterior communicating artery" J Cereb Blood Flow Metab. (in press). (1998)

[Publications] Mizuno Y, Ikebe S, Hattori N, Mochizuki Y, Hattori Y, Kondo T: "Movement Disorders.Neurologic principles and practice (Etiology of Parkinson's disease)" Watts RL,Koller WC,eds,The McGraw-Hill,New York, 161-182(21) (1997)

[Publications] 水野美邦, 池邊紳一郎: "ミトコンドリア病(Parkinson病と老化)" 埜中征哉, 後藤雄一編,医学書院,東京, 167-182(15) (1997)

[Publications] 小笠原洋治, 小澤敬也: "医学とサイエンスシリーズ(アデノ随伴ウイルス(AAV)ベクター)" 小澤敬也編,羊土社,東京, 66-71(6) (1997)

[Publications] Naoi M, Maruyama W, Dostert P: "Handbook of Endogenous Neurotoxins (An animal model of Parkinson's disease prepared by endogenous N-methyl (R) saloolinol)" Moser A,ed,Birkhauser,Boston, 41-61(21) (1997)

[Publications] Mizuno Y, Ikebe S, Hattori N, Mochizuki H, Hattori Y, Kondo T: "Movemet Disorders. Neurologic principles and practice (Etioloy of Parkinson's disease)" Watts RL,Koller WC,eds,The McGraw-Hill,New York, 161-182(21) (1997)

[Publications] 水野美邦, 池邊紳一郎: "ミトコンドリア病(Parkinson病と老化)" 埜中征哉, 後藤雄一編,医学書院,東京, 167-182(15) (1997)

[Publications] Kirino T: "Primer on Cerebrovascular Diseases (Ischemic tolerance in Welch KMA)" Caplan LR,Reis DJ,Siesjo BK,Welr B (Eds),Academic Press,San Diego, 240-243(4) (1997)

水野美邦順天堂大学, 医学部, 教授 (30049043)