運動系の分子生物機構ー運動制御の物質過程ー

• Project/Area Number: 01623002
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Research Institution: Nagoya University
• Principal Investigator: 永津 俊治 名古屋大学, 医学部, 教授 (40064802)
• Co-Investigator(Kenkyū-buntansha): 伊藤 正男 東京大学, 名誉教授 (90009887) ; 吉田 充男 自治医科大学, 教授 (70048966) ; 楢林 博太郎 順天堂大学, 名誉教授 (40052922) ; 杉田 秀夫 国立精神, 神経センター, 所長 (80009951) ; 鴨下 重彦 東京大学, 医学部, 教授 (60048973)
• Project Period (FY): 1989
• Project Status: Completed (Fiscal Year 1989)
• Budget Amount: ¥18,100,000 (Direct Cost: ¥18,100,000); Fiscal Year 1989: ¥18,100,000 (Direct Cost: ¥18,100,000)
• Keywords: 運動系 / 脳 / 筋肉 / 分子機構 / 発達 / 代謝 / 変性 / 情報伝達

Research Abstract

人類をはじめ、すべての動物の存在の最も具体的かつ最終的表現である運動の発現にかかわる要素である、中枢神経、末梢神経、筋肉よりなる運動系について、分子レベルの研究より、運動系の発達過程、運動系のエネルギー生産系の調節、運動系の代謝過程の遺伝子レベルでの調節、運動細胞の変性、老化・修復の機構、運動系細胞間の物質レベルでの情報伝達について研究を継続した。(1)運動系の発達とその異常の研究として、脳の発生から小児の運動機能の発達に至るまでの機構を、病理、生化学、分子遺伝学の側面から解析し統合すると同時に、特に運動発達の異常を細胞レベル、分子レベルで解明、(2)運動系における情報伝達の研究として、情報伝達の原理とその障害の機構を、脳のニューロン回路網と末梢運動神経系および筋肉なシナプスについて、シナプス前部伝達物質、シナプス後部の受容と情報変換機構を分子細胞レベルより解明、(3)運動系の分子・遺伝生物学的アプローチの研究として、ミトコンドリアの電子伝達系のエネルギー代謝機構とその異常、運動系細胞の固有な蛋白とその蛋白合成にかかわるDNAのモノクローナル抗体法とDNAシークエンスによる解明、運動系に異常をもつ遺伝性疾患のDNA上における異常などの研究、(4)運動系の変性と修復の成立過程の研究として、変性と修復の過程を、内因、外因、疫学的手法で追求し変性の結果生ずる異常を薬理学的手段を神経系の適応性とを用いて修復する基礎過程の分子レベルでの解析、(5)運動系における制御機構の研究として、運動系の統合中枢である錘体外路系等の機構を形態学、薬理学、生理学的手法でシナプスレベルで解明する。以上の研究を進め、遺伝性運動系疾患に関する遺伝子、運動系疾患の代表であるパーキンソン病モデル(サル)における組織の脳内移植法、運動疾患の脳内代謝課程のPETによる画像解析、運動系神経伝達物質関連酵素及び受容体のクローニングなどを研究した。

Research Products

• [Publications] Ichinose H.: "Isolation and characterization of a cDNA clone encoding human aromatic L-amino acid decarboxylase." Biochem.Biophys.Res.Commun. 164. 1024-1030 (1989)
• [Publications] Nagatsu T.: "The human tyrosine hydroxylase gene." Mol.Cell.Neurobiol.9. 313-321 (1989)
• [Publications] Ishii A.: "Ferrous ion activates the less active form of human adrenal tyrosine hydroxylase." Neurochem.Int.16. 59-64 (1990)
• [Publications] 鴨下重彦: "わが国における研究の展望" 神経研究の進歩. 33. 267-372 (1989)
• [Publications] Kamoshita S.: "Pontocerebellar hypoplasia associated with infantile motor neuron disease(Norman's disease)" Pediatric Pahtol.10. 133-142 (1990)
• [Publications] Igarashi T.: "Carrier detection of partial hypoxanthineguanine phosphoribosy transferase deficiency by analysis with BamHI restriction fragment length polymorphisms and oligonucleotide probes." Pediatric Res.(1990)
• [Publications] Fujimoto K.: "Impairment of passive and active avoidance produced kby destruction of the cholinergic projection from the pedunculopontine nucleus to the medial thalamus of the rat." Dementia.(1990)
• [Publications] Ito M.: "Long-term desensitization of quisqualate-specific glutamate receptors in Purkinje cells investigated with wedge recording from rat cerebellar slice." Neurosci.Res.7. 168-171 (1989)
• [Publications] Ito M.: "Long-term depression" Ann.Rev.Neurosci.12. 85-102 (1989)
• [Publications] Ito Y.: "Small-angle neutron scattering studies of the reconstituted TF1 of H+-ATPase from thermophilic bacterium PS3 with deuterated subunits." J.Mol.Biol.(1990)
• [Publications] Arahata K.: "Localization of nebulin,connectin(titin),and alpha-actinin in the skeletal muscle of Duchenne muscular dystrophy(DMD)." Neuroloty.38. 150 (1989)
• [Publications] Arahata K.: "Mosaic expression of dystrophin in symptomatic carriers of Duchenne's muscular dystrophy." N.Engl.J.Med.320. 138-142 (1989)
• [Publications] Arahata K.: "Dystrophin and the membrane hypothesis of musculardystrophy." TIPS.10. 437-439 (1989)
• [Publications] Nishi K.: "Difference in recovery patterns of striatal depamine content,tyrosine hydroxylase activity and total biopterin content after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridien(MPTP)administration:a comparison of young and older mice." Brain Res.489. 157-162 (1989)
• [Publications] Nishi K.: "Unresponsiveness to L-DOPA in parkinsonian patients:A study of homovanillic acid concentration in the cerebrospinal fluid." J.Neurol.Sci.92. 65-70 (1989)
• [Publications] Gibb W.R.G.: "New pathological observations in juvenile onset parkinsonism with dystoni a(dopa-responsive dystonia)." Neurology.(1989)
• [Publications] Yuzaki M.: "Multiple deletions in mitochondrial DNA at direct repeats of non-D-looop region in a familial mitochondrial myopathy." Biochem.Biophys.Res.Commun.(1989)
• [Publications] Sato H.: "Biochemical and pharmacological characterization of somatostatin receptors in rat brain." Res.Commun.Chem.Pathol.Pharmacol.(1989)
• [Publications] Ogawa N.: "Parkinsonism induced by indeloxazine hydrochloride." Clin.Therapeutics.(1989)
• [Publications] Ogawa N.: "Neurotransmitter and receptor alterations in rat persistent dyskinesia model induced by iminodipropionitrile." Eur.Neurol.(1989)
• [Publications] Tomura H.: "Novel regulatory enhancer in the gene of the humanmitochondrial ATP synthase beta subunit." J.Biol.Chem.(1990)
• [Publications] Okamoto H.: "Molecular characterization of mutant actin genes which induce heat-shock proteins in drosophila flight muscles." EMBO J.5. 589-596 (1986)
• [Publications] Fujita S.C.: "Quantitative tissue isolation from drosophila freeze-dried in acetone." J.Biochem.243. 97-104 (1987)
• [Publications] Okamoto H.: "Isolation of drosophila genomic clones homologous to the eel sodium channel gene." Proc.Jpn.Acad.Ser.B.63. 284-288 (1987)
• [Publications] Ono K.: "Monoclonal antibody that binds to both the prenatal and postnatal astroglia in rodent cerebellum." Developm.Brain Res.50. 154-159 (1989)
• [Publications] Ono K.: "Fetal hypothalamic brain garfts to the ventrmedial hypothalamic obese rats:an immunohistochemical,electrophysiological and behavioral study." Brain Res.Bull.(1990)
• [Publications] Kawamura K.: "Visual inputs to the dorsocaudal fastigial nucleus of the cat cerebellum.An experimental study using single unit recordings and horseradish peroxidase labelling." Arch.Ital.Biol.(1990)
• [Publications] Hata A.: "Direct evidence that the kinase activity of protein kinase C is involved in treanscriptional activation through a TPA-responsive element." FEBS Lett.252. 144-146 (1989)
• [Publications] Homma Y.: "Tissu- and cell specific expression of mRNAs for four types of inositol phospholipid-specific phosphlipase C." Biochem.J.164. 406-412 (1989)
• [Publications] Emori Y.: "A second type of rat phosphoinositide-sepcific phospholipase C ocntaining a src-related sequence not essential for phosphoinositide-hydrolyzing activity." J.Biol.Chem.(1989)
• [Publications] Kondo I.: "Exclusion mapping of the hereditary dentatorubropallidoluysian atrophy gene from Huntington's disease locus." J.Med.Genet.(1989)
• [Publications] Kanazawa I.: "Choreic movements in the macaque monkey induced by kainic aicd lesions of the striatum combines with L-DOPA:Pharmacological,biochemical and physiological studied on the neuronal mechanisms involved." Brain.(1989)
• [Publications] Suzuki K.: "Effects of tetrahydroisoquinoline on mitochondrial respiration.In:Alzheimer's and Parkinson's diseases" Nagatsu T.,Fisher A.,Yoshida M.eds.Plenum Press, (1990)
• [Publications] Yoshida M.: "Parkinosnism produced by an endogenous substance,tetrahydroisoquinoline,in monkeys and mice.In:Alzheimer's and parkinosn's disease" Nagatsu T.,Fisher A.,Yoshida M.eds.Plenum Press, (1990)
• [Publications] Ito M.: "Long-term depression in the cerebellum and its possible molecular mechanism.In:Brain Signal transduction and Memory" M.Ito and Y.Nishizuka eds.Academic Press, 199-212 (1989)
• [Publications] Kagawa Y.: "Stable oligomeric proteins for biosensors:protein chemistry,gene engineering and electronics.In:Bioinstrumentation" Developments and Applications Springer-Verlag, (1990)
• [Publications] Nagatsu T.: "Abnormalcatecholamine metabolism in spontaneously hypertensiverats volammetry in vivo.In:Progress in hypertension,vol.1," H.Saito(Ed.).VNU Science Press,Utrecht,1-8 (1989)
• [Publications] Nagatsu T.: "Regulation of catecholamine synthesis by tetrahydrobiopterin as cofactor of tyrosine hydroxylase.In:Progress in Catecholamine Research," A.Dahlstrom,R.H.Belmaker and M.Sandler(Eds.)Alanb R.Liss,Inc.,New York,41-46 (1989)
• [Publications] Nagatsu T.: "Molecular genetic approaches to the study of human catecholamine-synthesizing enzymes.In:Bioinformatics," O.Hatase,J.H.Wang(Eds.).Elsevier Science Publishers B.V.,Amsterdam,281-288 (1989)
• [Publications] Kojima K.: "Microbore HPLC for biological samples:catecholamines,peptides and proteins.In:PROGRESS IN HPLC,Vol.4," M.Yoshioka,S.Parvez,H.Parvez.(Eds.).VNU Science Press,Utrecht,211-227 (1989)
• [Publications] Nagatsu T.: "Inhibitors and stimulatorsnof monoamine-synthesizing enzymes from microbes.In:Horizons on Antibiotic Research," B.D.Davis et al.(Eds.).Japan Antibiotics Research association,Tokyo,121-137 (1989)
• [Publications] Nagatsu T.: "Physiological and clinical chemistry of biopterin.In:Medical Research Reviews," G.deStevens(Ed.).John Wiley&Sons,New York,25-44 (1989)
• [Publications] Nagatsu T.: "Roles of calcium ion in the regulation of tyrosine hydroxylase.In:Calcium protein signaling," H.Hidaka,E.Carafoli,A.R.Means and T.Tanaka(Eds.)Plenum Publishing Corporation,New York,425-433 (1989)
• [Publications] Nakajima T.: "Neuron-specific enolase and aromatic L-amino acid decarboxylase;neuroendocrine makers in immunohistochemistry.In:Endocrine pathology update," J.Lechago and T.Kameya(Eds.).Neuroendocrine Markers,Field and Wood,Inc.,Philadelphia,277-292 (1989)