大脳辺縁系における情動・記憶・免疫系の相互干渉機構の解明

2001 Fiscal Year Annual Research Report

• Project/Area Number: 12210009
• Research Institution: Toyama Medical and Pharmaceutical University
• Principal Investigator: 小野 武年 富山医科薬科大学, 医学部, 教授 (50019577)
• Co-Investigator(Kenkyū-buntansha): 倉知 正佳 富山医科薬科大学, 医学部, 教授 (80019603) ; 村口 篤 富山医科薬科大学, 医学部, 教授 (20174287) ; 西条 寿夫 富山医科薬科大学, 医学部, 教授 (00189284) ; 大谷 修 富山医科薬科大学, 医学部, 教授 (90127548) ; 許 南浩 岡山大学, 大学院・医歯学総合研究科, 教授 (70173573)
• Keywords: 情動 / 記憶 / 認知 / 免疫 / 大脳辺縁系 / ニューロン活動 / サイトカイン / 行動

Research Abstract

I.神経生理学的研究:ラット視床の感覚副経路中継核には、1)過去の報酬体験に依存して応答する潜時の速い応答と、2)報酬を報酬が得られる直前で最大応答を示し、報酬予測に関与する潜時の遅い応答の2つの複合的応答を示すニューロンが相当数存在することを明らかにした。これらの結果は、視床の副経路中継核(視床後外側核、内側膝状体帯部領域)が過去の報酬体験と将来の報酬予測を符号化していることを示唆し、従来大脳で処理されていると考えられていた記憶や予測などの認知機能が、視床レベルでも行われている可能性があることを初めて示したものである。
II.神経解剖学的研究:ラット扁桃体の基底外側核のGABA作動性ニューロンはノルアドレナリン作動性ニューロンから非対称性-興奮性シナプスを受け,GABA作動性ニューロンから対称性-抑制性シナプスを受けることを明らかにした。
III.分子生物学的研究:小脳、海馬、視床に発現する新規遺伝子Calminがアクチンに結合し、Post-synaptic densityの分画に含まれることを明らかにした。
IV.神経免疫学的研究:RT-PCR法により、免疫物質であるインターロイキン(IL)-18(IL-18)のmRNAが嗅球、皮質、海馬、線条体、視床下部、小脳、橋延髄に発現していること、さらにin situ hybridization法により、脳内でIL-18を発現している細胞はミクログリア細胞であることなどを明らかにした。

Research Products

• [Publications] Yamaguchi, H., Tamura, R., Kuriwaki, J., Eifuku, S., Ono, T.: "Effects of T-588, a newly developed cognitive enhancer compound on synaptic plasticity in the dentate gyrus of freely moving rats"J.Pharmacol.Exp.Ther.. 298. 354-361 (2001)
• [Publications] Komura, Y., Tamura, R., Uwano, T., Nishijo, H., Kaga, K., Ono, T.: "Retrospective and prospective coding for predicated reward in the sensory thalamus"Nature. 412. 546-549 (2001)
• [Publications] Nakada, Y., Tamura, R., Kimura, T., Uwano, T., Nishijo, H., Ono, T.: "Ameliorative effects of a cognitive enhancer, T-588, on place learning deficits induced by transient forebrain ischemia in rats"Physiol.Behav.. 74. 1-9 (2001)
• [Publications] Nishimura, T.F., Fukunaga, T., Nishijo, H., Ono, T., Kajiura, H., Yokomukai, Y.: "Electroencephalogram spectral characteristics after alcohol ingestion in Japanese men with aldehyde dehydrogenase-2 genetic variations : comparison with perirheral changes. Alcohol"Clin.Exp.Res.. 25. 1030-1036 (2001)
• [Publications] Kamiyama, H., Kurimoto, M., Yamamura, J., Uwano, T., Hirashima, Y., Kurokawa, M., Endo, S., Shiraki, K.: "Effect of immunity on gene delivery into anterior horn motor neurons by live attenuated herpes simplex virus vector"Gene Ther.. 8. 1180-1187 (2001)
• [Publications] Li, R., Nishijo, H., Wang, Q., Uwano, T., Tamura, R., Ohtani, O., Ono, T.: "Light and electron microscopic study of cholinergic and noradrenergic elements in the basolateral nucleus of the rat amygdala : evidence for interactions between the two systems"J.Comp.Neurol.. 439. 411-425 (2001)
• [Publications] Ohtani, Y., Ohtani, O.: "Postnatal development of lymphatic vessels and their smooth muscle cells in the rat diaphragm : A confocal microscopic study"Arch.Histol.Cytol.. 106(Suppl.1,No.2). 251-259 (2001)
• [Publications] Yamamoto, T., Matsuda, T., Junicho, A., Kishi, H., Yoshimura, A., Muraguchi, A.: "Hematopoietic cell-specific adapter proteins, SLP-76 and BLNK, effectively activate NF-AT as well as NF-κB by Syk and Tec PTKs in non-lymphoid cell lines"FEBS Lett.. 491. 272-278 (2001)
• [Publications] Yamamoto, T., Matsuda, T., Muraguchi.A., Miyazono, K., Kawabata, M.: "Cross-talk between IL-6 and TGF-β signaling in hepatoma cells"FEBS Lett.. 492. 247-253 (2001)
• [Publications] Matsuda, T., Junicho, A., Yamamoto, T., Kishi, H., Korkimaz, K., Saatciogl u F., Fuse, H., Muraguchi, A.: "Cross-talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells"Biochem.Biophys.Res.Commun.. 283. 179-187 (2001)
• [Publications] Yoshino, T., Kishi, H., Nagata, T., Tsukada, K., Saito, S., Muraguchi, A.: "Differential involvement of p38 MAP kinase pathway and Bax translocation in the mitochondria-mediated cell death in TCR-and dexamethasone-stimulated thymocytes"Eur.J.Immunol.. 31. 2702-2708 (2001)
• [Publications] Matsuda, T., Yamamoto, T., Muraguchi, A., Saatcioglu, F.: "Cross-talk between transforming growth factor-β and estrogen receptor signa ling through Smad3"J.Biol.Chem.. 276. 42908-42914 (2001)
• [Publications] Ono, T., Nishijo, H.: "Hippocampal role in cognitive functions and memory, and effects of a novel cognitive enhancer on learning deficits due to hippocampal lesions"Psychogeriatrics. 1. 277-286 (2001)
• [Publications] Li, R.-X., Nishijo, H., Ono, T., Ohtani, Y., Ohtani, O.: "Synapses on GABAergic neurons in the basolateral nucleus of the rat amygdala : Double-labeling immunoeletron microscopy"Synapse. 43. 42-50 (2002)
• [Publications] Hori, E., Uwano, T., Tamura, R., Miyake, N., Nishijo, H., Ono, T.: "Effects of a novel arginine-vasopressin derivative, NC-1900, on the spatial memory impairment of rats whh transient forebrain ischemia"Cognitive Brain Res.. (in press). (2002)
• [Publications] Toyomitsu, Y., Nishijo, H., Uwano, T., Kuratsu, J., Ono, T.: "Neuronal responses of the rat amygdala during extinction and reassociation learning in the elementary and configural associative tasks"Eur.J.Neurosci.. (in press). (2002)
• [Publications] Hori, E., Tabuchi, E., Matsumura, N., Tamura, R., Eifuku, S., Endo, S., Nishijo, H., Ono, T.: "Representation of place by monkey hippocampal neurons in real and virtual translocation"Hippocampus. (in press). (2002)
• [Publications] 小野武年, 西条寿夫, 山口英俊, 上野照子: "ラット海馬体CA1錐体細胞層における細胞外集合スパイク電位に対する粗サポニン分画の抑制機構"The GINSENG REVIEW. 29. 22-29 (2002)
• [Publications] Sumiyoshi, T., Matsui, M., Yamashita, I., Nohara, S., Uehara, T., Kurachi, M., Sumiyoshi, S., Meltzer, H.Y.: "The effect of tandospirone, a serotonin 1 A agonist on memory function in schizophrenia"Biol. Psychiatry. 15. 861-868 (2001)
• [Publications] Sumiyoshi, C., Matsui, M., Sumiyoshi, T., Yamashita, I., Sumiyoshi, S., Kurachi, M.: "Semantic structure in schizophrenia as assessed by the category fluency test : effect of verbal intelligence and age of onset"Psychiatry Res.. (in press). (2002)
• [Publications] Murata, M., Kashiwa, A., Oshima, A., Umino, A., Kurachi, M., Nishikawa, T.: "Nomifensine-induced c-fos mRNA expression in discrete brain areas of the developing rat"Neuroscience Letters. 303. 99-102 (2001)
• [Publications] Tajiri, K., Emori, K., Murata, M., Tanaka, K., Suzuki, M., Uehara, T., Sumiyoshi.T., Kurachi, M., Ashby Jr., C.R.: "The intracerebroventricular administration of NMDA-Rl antisense oligodeoxynucleotide significantly alters the activity of ventral tegmental area dopamine neurons : an electrophysiological study"Synapse. 40. 275-281 (2001)
• [Publications] Kataoka, K., Nakajima, A., Takata, Y., Saito, S., Huh, N.: "Screening for genes involved in tissue invasion based on placenta formation and cancer cell lines with low and high metastatic potential"Cancer Lett.. 163(2). 213-219 (2001)
• [Publications] Jiang, H.X., Pu, H., Huh, N.H., Yokota, K., Oguma, K., Namba, M.: "Helicobacter pylori induces pepsinogen secretion by rat gastric cells in culture via a cAMP signal pathway"Int.J.Mol.Med.. 7(6). 625-629 (2001)
• [Publications] Aso, M., Suzuki, M., Kawasaki, Y., Hagino, H., Kurokawa, K., Yuasa, S., Kurachi, M.: "Sylvian fissure and inferior horn enlargement in patients with schizophrenia : A magnetic resonance imaging study"Psychiatry Clin.Neurosci.. 55. 49-56 (2001)
• [Publications] Hagino, H., Suzuki, M., Mori, K., Kurokawa, K., Yotsutsuji, T., Kurachi, M., Seto, H.: "Magnetic Resonance Imaging Study of Cavum Septi Pellucidi in Patients with Schizophrenia"Am.J.Psychiatry. 158. 1717-1719 (2001)
• [Publications] Takahashi, T., Kawasaki, Y., Kurokawa, K., Hagino.H., Nohara, S., Yamaishita, I., Nakamura, K., Murata, M., Matsui, M., Suzuki, M., Seto, H., Kurachi, M.: "Lack of normal structural asymmetry of the anterior cingulate gyrus in female patients with schizophrenia : a volumetric magnetic resonance imaging study"Schizophrenia Res.. (in press). (2002)
• [Publications] Suzuki, M., Nohara, S., Hagino, H., Yotsutsuji, T., Kurokawa, K., Kawasaki, Y., Matsui, M., Watanabe, N., Seto, H., Kurachi, M.: "Regional changes in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI"Schizophrenia Res.. (in press). (2002)
• [Publications] Matsui, M., Yoneyama, E., Sumiyoshi, T., Noguchi, K., Nohara, S., Suzuki, M., Kawasaki, Y., Seto, H., Kurachi, M.: "Lack of self-control as assessed by a personalitu inventory is related to reduced volume of supplementary motor area"Psychiatry Res.Neuroimaging. (in press). (2002)
• [Publications] Sumiyoshi, T., Matsui, M., Nohara, S., Yamashita, I., Kurachi, M., Sumiyoshi, C., Jayathilake, K., Meltzer, H.: "Addition of tandospirone to neuroleptic treatment enhances cognitive performance in schizophrenia"Am.J.Psychiatry. 158. 1722-1725 (2001)
• [Publications] Kamiyama, H., Kurimoto., M., Yamamura, J., Uwano, T., Hirashima, Y., Kurokawa, M., Endo, S., Shiraki K.: "Effect of immunity on gene delivery into anterior horn motor neurons by live attenuated herpes simplex virus vector"Gene Therapy. 8. 1180-1187 (2001)
• [Publications] Takasaki, I., Andoh, T., Nojima.H., Shiraki, K., Kuraishi, Y.: "Gabapentin antinociception in mice with acute herpetic pain induced by herpes simplex virus infection"J.Pharmcol.Experi.Therapeu.. 296. 70-75 (2001)
• [Publications] Honda, M., Okuda, T., Hasegawa, T., Kurokawa, M., Shiraki, K., Matsuo, K., Komatsuzaki, M., Niimura, M.: "Effect of long-term, low-dose acyclovir suppressive therapy on herpes simplex virus type 2 susceptibility to acyclovir and frequency of acyclovir-resistance"Antiviral Chem.Chemother. 12. 243-249 (2001)
• [Publications] Koti-Tsekpo, M.W., Rukunga, G.M., Kurokawa, M., Kageyama, S., Mungai, G.M., Muli, J.M., Muthaura, C.N., Kanyara, J.N., Tukei, P.M., Shiraki, K.: "An in vitro evaluation of extracts from some medicinal plants in Kenya against herpes simplex virus"Afri.J.Health Sci.. 8. 61-69 (2001)
• [Publications] Kamiyama, T., Kurokawa, M., Shiraki, K.: "Characterization of the DNA polymerase gene of varicella-zoster viruses むresistant to acyclovir"J.General Virol.. (in press). (2002)
• [Publications] Kageyama, S., Yamada, K., Kurimura, T., Shiraki, K.: "Polymorphism of CCR5 affecting HIV disease progression in the Japanese population"AIDS Res.Human Retroviruses. 17. 991-995 (2001)
• [Publications] Ishisaki, Z., Takaishi, M., Furuta, I., Huh, N.H.: "Calmin, a protein with calponin homology and transmembrane domains expressed in maturing spermatogenic cells"Genomics. 74(2). 172-179 (2001)
• [Publications] Yamago, G., Takata, Y., Furuta, I., Urase, K., Momoi, T., Huh, N.: "Suppression of hair follicle development inhibits induction of sonic hedgehog, patched, and patched-2 in hair germs in mice"Arch.Dermatol.Res.. 293(9). 435-441 (2001)
• [Publications] Niino, Y.S., Irie, T., Takaishi, M., Hosono, T., Huh, N., Tachikawa, T., Kuroki, T.: "PKC-II, a new isoform of potein kinase C specifically exrpessed in the seminiferous tubules of mosue testis"J.Biol.Chem.. 276(39). 36711-36717 (2001)
• [Publications] Kondo, A., Sakaguchi, M., Makino, E., Namba, M., Okada, S., Huh, N.: "Decrease in S100C expression in various human tissues after malignant transformation"Acta Med.Okayama. (in press). (2001)
• [Publications] Makino, T., Takaishi, M., Morohashi, M., Huh, N.: "Hornerin, a novel profi laggrin-like protein and differentiation-specitic marker isolated from mouse skin"J.Biol.Chem.. 276(50). 47445-47452 (2001)
• [Publications] Inoue, Y., Miyazaki, M., Tsuji, T., Sakaguchi, M., Fukaya, K., Huh, N.H., Namba, M.: "Reactivation of liver-specific gene expression in an immortalized human hepatocyte cell line by introduction of the human HNF4alpha2 gene"Int.J.Mol.Med.. 8(5). 481-487 (2001)
• [Publications] Yokoyama, T., Ayabe, S., Miyagi, H., Sugano, T., Otsu, A., Sato, H., Kageyama, S., Fujii, T., Shiraki, K.: "Varicella-zoster virus gH : gL contains a structure reactive with the anti-human gamma chain of IgG near the glycosylation site"J.General Virol.. 82. 331-334 (2001)
• [Publications] Kurokawa, M., Hozumi, T., Tsurita, M., Kadota, S., Namba, T., Shiraki, K.: "Biological characterization of eugeniin as an anti-herpes simplex virus type 1 compound in vitro and in vivo"J.Pharmacol.Experi.Therapeu.. 297. 372-379 (2001)
• [Publications] 田積徹, 小野武年, 西条寿夫: "不安の大脳生理学"分子精神医学. (印刷中).
• [Publications] Tsurita, M., Kurokawa, M., Imakita, M., Fukuda, Y., Watanabe, Y., Shiraki, K.: "Alleviation of influenza infection by early augmentation of interleukin (IL)-12 level in the airway of mice administered orally with clarithromycin or intranasally with IL-12"J.Pharmacol.Experi.Therapeu.. 298. 362-368 (2001)
• [Publications] Kamiya, N., Asano, Y., Yoshino, J., Sasaki, K., Honma, Y., Kawase, H., Yokochi, T., Shiraki, K., Tsuji, T.: "Long-term persistence of cellular immunity to Oka vaccine virus induced by pernasal co-administration with Escherichia coli enterotoxin in mice"Vaccine. 19. 3131-3136 (2001)
• [Publications] Shiraki, K., Sato, H., Yoshida, Y., Yamamura, J., Tsurita, M., Kurokawa, M., Kageyama, S.: "Construction of Oka varicella vaccine expressing human immunodeficiency virus env antigen"J.Medical Virol.. 64. 96-103 (2001)
• [Publications] Hasegawa, T., Kawana, T., Okuda, T., Tsukada, T., Horii, M., Shiraki, K.: "Analysis of herpes simplex virus isolated from the genital lesions since 1977 in Japan"J.Medical Virol.. 63. 57-63 (2001)
• [Publications] Takahashi, M., Kamiya, H., Asano, Y., Shiraki, K., Baba, K., Otsuka, T., Hirota, T., Yamanishi, K.: "Immunization of the elderly to boost immunity against varicella-zoster virus (VZV) as assessed by VZV skin test reaction"Archi.Virol.. (Suppl)17. 161-172 (2001)
• [Publications] Sasaki, K., Asano, Y., Honma, Y., Kamiya, N., Hanada, T., Ichinose, Y., Yokochi, T., Shiraki, K., Tsuji.T.: "Adjuvant action of Escherichia coli enterotoxin for delayed type hypersensitivity to Oka varicella virus on pernasal co-administration in mice"Vaccine. 19. 931-936 (2001)
• [Publications] Tamura, R., Ono, T.: "Neural substrate for spatial memory in the monkey hippocampus. In Neuroscientific Basis of Dementia, by Tanaka, C., McGeer, P.L.and Ihara, Y.(Ed.)"Birkhauser Verlag Basel, Switerland. 43-48 (2001)
• [Publications] 小野武年, 西条寿夫: "第7章 総合機能,B.情動と動機づけ,「標準生理学第5版」本郷利憲, 廣重力監修, 豊田順一, 熊田衛, 小澤靜司, 福田康一郎, 本間研一編集"医学書院,東京. 437-441 (2001)
• [Publications] 小野武年: "第6章 自律機能と本能行動,II.視床下部と辺縁系.「標準生理学第5版」本郷利憲, 廣重力監修, 豊田順一, 熊田衛, 小澤靜, 福田康一郎, 本間研一編集"医学書院,東京. 407-423 (2002)
• [Publications] 小野武年: "第2部 学ぶ脳,2.好きこそものの上手なれ.「育つ・学ぶ・癒す 脳図鑑21」伊藤正男序文,小泉英明編著"工作舎,東京. 237-270 (2001)
• [Publications] 小野武年, 西条寿夫: "第7章 総合機能,C.学習と記憶.「標準生理学第5版」本郷利憲, 廣重力監修, 豊田順一, 熊田衛, 小澤靜司, 福田康一郎, 本間研一編集"医学書院,東京. 441-446 (2001)
• [Publications] 小野武年, 西条寿夫: "大脳辺縁系・大脳基底核における情と意の出力機構-本能、情動、生きる喜び-「情と意の脳科学-人とは何か」松本 元編集"培風館,東京(印刷中). (2002)
• [Publications] 西条寿夫, 小野武年: "情と意における大脳辺縁系と連合野の役割-生物学的価値評価、行動戦略の決定-「情と意の脳科学-人とは何か」松本 元編集"培風館,東京(印刷中). (2002)
• [Publications] 上野照子, 小野武年: "第12章 扁桃体を情動.セラピストのための基礎研究論文集 (4)「人間行動と皮質下機能」第3部大脳辺縁系と情動・動機づけ、永井洋一編集"協同医書出版社,東京(印刷中). (2002)
• [Publications] 西条寿夫, 小野武年: "第10章 情動のメカニズムと大脳辺縁系.セラピストのための基礎研究論文集 (4)「人間行動と皮質下機能」第3部大脳辺縁系と情動・動機づけ、永井洋一編集"協同医書出版社,東京(印刷中). (2002)
• [Publications] 西条寿夫, 堀悦郎, 小野武年: "食物のおいしさと食欲の調節機構.「フードデザイン21」荒井綜,川端晶子,茂木信太郎,山野井昭雄編集"サイエンスフォーラム(株),東京(印刷中). (2002)
• [Publications] 小野武年: "情動,脳神経科学(Neuroscience)金澤一郎,篠田義一,廣川信隆,御子柴克彦,宮下保司 編集"三輪書店,東京(印刷中). (2002)