1996 Fiscal Year Annual Research Report

遺伝性多飲マウスにおける神経内分泌・免疫異常の解析と環境ストレス応答モデルの開発

Research Project

Project/Area Number	07507004
Section	試験
Research Institution	University of Occupational and Environmental Health, Japan
Principal Investigator	山下博産業医科大学, 医学部, 教授 (00030841)
Co-Investigator(Kenkyū-buntansha)	椛島成利産業医科大学, 医学部, 助手 (80279322) 上田陽一産業医科大学, 医学部, 講師 (10232745) 澁谷泉産業医科大学, 医学部, 助教授 (50162649) 稲永清敏九州歯科大学, 歯学部, 教授 (90131903) 大磯ユタカ名古屋大学, 医学部, 講師 (40203707) 山下優毅産業医科大学, 医学部, 教授 (00028680) 河田光博京都府立医科大学, 医学部, 教授 (60112512) 河南洋宮崎医科大学, 医学部, 教授 (00049058) 堀哲郎九州大学, 医学部, 教授 (00022814)
Keywords	遺伝性多飲マウス / バゾプレシン / V2受容体遺伝子 / DNA合成能 / NK細胞活性 / オキシトシン / 抗利尿効果 / 上喉頭神経
Research Abstract	遺伝性多飲マウス(STR/N)の病態および種々の機能異常の解析を行い、以下の成績を得た。 1.分子生物学的解析:STR/Nのバゾプレシンの遺伝子には塩基配列において一カ所の異常がみれらたものの、アミノ酸配列には異常はなかった。さらに正常マウス(ICR)とSTR/NのV2受容体遺伝子の構造決定を行ったところSTR/NのV2受容体遺伝子構造には異常が認められなかった。 2.行動学的解析:Passive Avoi dance法ならびにShuttle Avoi dance法を用いてSTR/NとICRの学習能力を解析したところ、両試験において、STR/NマウスはICRマウスに比較して、学習能力が優れていることが示唆された。 3.免疫学的解析:In vivoの免疫及びIn vitroの細胞培養系を用いてSTR/Nの免疫機能を更に検討し、以下の結果を得た。(1)コントロールのICR及びC3H/HeNマウスに比べて、STR/Nの胸腺細胞数は増加、脾細胞数は減少していた。(2)胸腺細胞、脾細胞をin vitroで培養し、その機能を検討すると、ConA,SEAなどによる非特異的T細胞のDNA合成能は、STR/Nマウスで増強されていたが、ダニ抗原刺激による、特異的T細胞のDNA合成能は低下していた。(3)血清中のTotal lgは、両者問でほとんど差が見られなかったが、ダニ抗原で免疫した後に見られる特異的抗体の産生能は、STR/Nで低下していた。(4)脾臓のNK細胞活性もSTR/Nで低下していた。(5)バゾプレッシン、オキシトシンは、正常マウスのNK細胞活性を濃度依存性に抑制した。(6)以上のことより、STR/Nでは免疫機能に異常があり、この異常がバゾプレッシン、オキシトシンと関連があることが示唆された。 4.生理学的解析:バゾプレシンのV2受容体以降の情報伝達系について検討した結果、STR/Nにおいて高濃度のバゾプレシンは抗利尿効果を示し、phosphodi ester ase inhibitorによっても抗利尿効果が認められた。さらにバゾプレシンに対してのcAMP産生能においてもSTR/NとICRで統計学的に有意な差異は認められなかった。 5.電気生理学的解析:STR/NとICRを用いて、上喉頭神経の末梢端から神経束応答を記録した結果、STR/NよりICRの放電数は有意に高かった。またスライスパッチクランプ法を用いてマウス視索上核ニユーロンへのシナプス入力を検討したとこと、(1)主要なシナプス入力はグルタミン酸を介する興奮性入力とGABAを介する抑制性入力であること、(2)μおよびχオピオイドがシプナス前膜に働き伝達物質の放出を抑制していることが解った。

Research Products

(39 results)

All Other

All Publications (39 results)

[Publications] Kannan,H.et al.: "Activation of sympathetic outflow by recombinant human interleukin-1β in conscious rats." Am.J.Physiol.270. R479-R485 (1996)
[Publications] Tanaka,H.et al.: "Biphasic changes in behavioral,endocrine,and sympathetic systems in adjuvant arthritis in Lewis rats." Brain Res.Bull.39. 33-37 (1996)
[Publications] Knnan,H.et.al.: "Changes in renal sympathetic nerve activities in the regulation of body fluid balance with special reference to central neuropetides in conscious rats." Jpn.J.Physiol.46. 111-122 (1996)
[Publications] Hanamori,T.et al.: "Fiber types of the lingual branch of the trigeminal nerve,chorda tympani,lingual-tonsillar and pharyngeal branches of the glossopharyngeal nerve,and superior laryngeal nerve and their relation to the cardiovascular responses in rats." Neurosci.Lett.219. 49-52 (1996)
[Publications] Ishizuka,Y.et al.: "Effects of area postrema lesion and abdominal vagotomy on interleukin-1β-induced norepinephrine release in the hypothalamic paraventricular nucleus region in the rat." Neurosci.Lett.(in press). (1996)
[Publications] Kannan,H.et al.: "Effects of systemic interleukin-1β administration on daily drinking and renal excretory function in conscious rats." Physiol.Behav.(in press). (1996)
[Publications] 斉田光彦et al.: "アドレノメデュリンと自律神経活動" 現代医療. 28. 2841-2844 (1996)
[Publications] 花森隆充et al.: "ラット島皮質ニューロンの咽頭・喉頭領域の味刺激に対する応答" 日本味と匂学会誌. 3. 480-483 (1996)
[Publications] Inenaga,K.et al.: "Osmotic modulation in glutamatergic excitatory synaptic inputs to neurons in the supraoptic nucleus of rat hypothalamus in vitro." J.Neuroendocrinol.63 (1997)
[Publications] Myozaki,M.et al.: "Induction of autoimmune hepatitis and autoantibodies to liver antigens by neonatal thymectomy in mice" Clin.Exp.Imm unol.104. 133-143 (1996)
[Publications] Fujii,S.et al.: "B cell mitogenic activity of house dust mite,Dermatophagoides farinae,antigens." Immunol.Letter. 49. 37-42 (1996)
[Publications] Kishi,H.et al.: "Proliferation of retinal pigment epithelial cells by neuropeptides in vitro." Curr.Eye Res.15. 708-713 (1996)
[Publications] Ueda,S.et al.: "Organization of regenerating serotonergic fibers in the hippocampal formation." Brain Res. Bull.39. 89-99 (1996)
[Publications] Pasterkamp R.J.et al.: "The perinatal ontogeny of estrogen receptor-immunorectivity in the depeloping male and female rat hypothalamus." Dev.Brain Res.91. 300-303 (1996)
[Publications] Hu、A.et al.: "Exposure of postnatal rats to glucocorticoids suppresses the development of choline acetyltransferase-immunoreactive neurons : role of adrenal steroids in the development of forebrain cholinergic neurons." J.Chem.Neuroanat.10. 1-10 (1996)
[Publications] Morimoto,M.et al.: "Phenotypic alterations of neuropeptide Y,vasoreactive interstinal peptide and cholone acetyltransferase in rat cultured cromaffin cells as effected by nerve growth factor and glucocorticoid." Arch.Histol.Cytol.59. 205-218 (1996)
[Publications] Ueda,S et al: "Altertion of serotonergic innervation in the suprachiasmatic nucleus of the rat following removal of input fibers from retina and lateral geniculatenucleus." Neurosci.Lett.211. 97-100 (1996)
[Publications] Yang, M.et al.: "The effects of nerve growth factor on newborn rat dosal root ganglion neurons in vitro." J.Brain Res.37. 313-317 (1996)
[Publications] Visser,D.T.M.et al.: "The alteration of glucocorticoid recepter-immunoreactivity in the rat forebrain following short-term and long-term adrenalectomy." Brain Res.729. 216-222 (1996)
[Publications] Ueda,S.et al: "Neuro-glial neurotrophic inteeraction in the S-100β retarded mutant mouse(Polydactyly Nagoya)." Brain Res.738. 15-23 (1996)
[Publications] Morimoto,M et al.: "Distribution of glucocorticoid receptor immunoreactivity and mRNA in the rat brain : an immunohistochemical and in situ hybridization study." Neurosci.Res. 26. 235-269 (1996)
[Publications] 堀哲郎et al.: "発熱の病体生理" Today's Therapy. 20. 115-118 (1996)
[Publications] Uchimura,D.: "Facilitatory effects of pituitary adenylate cyclase activating polypeptide(PACAP) on neurons in the magnocellular portion of the rat hypothalamic paraventricular nucleus(PVN) in vitro.21GC23:J.Neuroendocrinol" 8. 137-143 (1996)
[Publications] Li,A-J: "Fibroblast growth factor receptor-1 in the lateral hypothalamic area regulates food intake." Exptl.Neurol.137. 318-323 (1996)
[Publications] Shimizu,N: "Immoblization increases noradrenaline release and reduces NK cytotoxicity in spleen of conscious rat." Am.J.Physiol.271. R537-R544 (1996)
[Publications] Mo,Z.L.: "The effects of IL-1β on neuronal activities in the dorsal motor nucleus of the vagus in rat brain slices." Brain Res.Bull. 41. 249-255 (1996)
[Publications] Oka,T.: "Intracerebroventricular injection of tumor necrosis factor α induces thermal hyperalgesia in rats." Neuroimmunomodulation. 3. 135-140 (1996)
[Publications] Oka,T.: "Inhibition of peripheral interleukin-1-β-induced hyperalgesia by the intracerebroventricular administrationof diclofenac and α-melanocyte-stimulating horm one." Brain Res.736. 237-242 (1996)
[Publications] Oka,K: "The AV3V neurons which send axons to hypothalamic nuclei respond to the systemic injection of 1L-1β." Am.J.Physiol.(in press). (1997)
[Publications] Oka,T.: "Biphasic alteration in the trigeminal nociceptive neuronal responses after intracerebroventricular injection of prostaglandin E2 in rats." Brain Res.(in press). (1997)
[Publications] Li,A.J.: "Interleukin-6 inhibits long-term potentiation in rat hippocampal slices." Brain Res.(in press). (1997)
[Publications] Katafuchi,T.: "Differential effects of tumor necrosis factor-α and-β on the rat ventromedial hypothalamic neurons in vitro." Am.J.Physiol.(in press). (1997)
[Publications] 片渕俊彦: "交感神経による脾臓ナチュラルキラー細胞活性制御の視床下部機序" 自律神経. 33. 267-272 (1996)
[Publications] 岡孝和: "痛みと情動" Clinical Neuroscience. 14. 1025-1027 (1996)
[Publications] 河田光博et al.: "現代の神経内分泌学" 下垂体後葉ホルモンの産生、分布、分泌機能, 179-186 (1996)
[Publications] Hori,T.: "Discussion on Future Directions in Psychoneuroimmunology and Cancer." Nishimura Co.,Ltd.and Smith-Gordon Co.,Ltd., 166 (1996)
[Publications] Hori,T.: "Physiological Basis of Occupational Health : Stressful Environments." SPB Academic Publishing bv, 278 (1996)
[Publications] 堀哲郎: "現代の神経内分泌学" メディカル・サイエンス・インターナショナル, 506 (1996)
[Publications] 堀哲郎: "最新内科学大系、PartI.内科総論部門、第2巻「科学としての内科学」" 中山書店, 372 (1996)

1996 Fiscal Year Annual Research Report

遺伝性多飲マウスにおける神経内分泌・免疫異常の解析と環境ストレス応答モデルの開発

Principal Investigator

山下 博 産業医科大学, 医学部, 教授 (00030841)

Research Products

[Publications] Kannan,H.et al.: "Activation of sympathetic outflow by recombinant human interleukin-1β in conscious rats." Am.J.Physiol.270. R479-R485 (1996)

[Publications] Tanaka,H.et al.: "Biphasic changes in behavioral,endocrine,and sympathetic systems in adjuvant arthritis in Lewis rats." Brain Res.Bull.39. 33-37 (1996)

[Publications] Knnan,H.et.al.: "Changes in renal sympathetic nerve activities in the regulation of body fluid balance with special reference to central neuropetides in conscious rats." Jpn.J.Physiol.46. 111-122 (1996)

[Publications] Ishizuka,Y.et al.: "Effects of area postrema lesion and abdominal vagotomy on interleukin-1β-induced norepinephrine release in the hypothalamic paraventricular nucleus region in the rat." Neurosci.Lett.(in press). (1996)

[Publications] Kannan,H.et al.: "Effects of systemic interleukin-1β administration on daily drinking and renal excretory function in conscious rats." Physiol.Behav.(in press). (1996)

[Publications] 斉田光彦et al.: "アドレノメデュリンと自律神経活動" 現代医療. 28. 2841-2844 (1996)

[Publications] 花森隆充et al.: "ラット島皮質ニューロンの咽頭・喉頭領域の味刺激に対する応答" 日本味と匂学会誌. 3. 480-483 (1996)

[Publications] Inenaga,K.et al.: "Osmotic modulation in glutamatergic excitatory synaptic inputs to neurons in the supraoptic nucleus of rat hypothalamus in vitro." J.Neuroendocrinol.63 (1997)

[Publications] Myozaki,M.et al.: "Induction of autoimmune hepatitis and autoantibodies to liver antigens by neonatal thymectomy in mice" Clin.Exp.Imm unol.104. 133-143 (1996)

[Publications] Fujii,S.et al.: "B cell mitogenic activity of house dust mite,Dermatophagoides farinae,antigens." Immunol.Letter. 49. 37-42 (1996)

[Publications] Kishi,H.et al.: "Proliferation of retinal pigment epithelial cells by neuropeptides in vitro." Curr.Eye Res.15. 708-713 (1996)

[Publications] Ueda,S.et al.: "Organization of regenerating serotonergic fibers in the hippocampal formation." Brain Res. Bull.39. 89-99 (1996)

[Publications] Pasterkamp R.J.et al.: "The perinatal ontogeny of estrogen receptor-immunorectivity in the depeloping male and female rat hypothalamus." Dev.Brain Res.91. 300-303 (1996)

[Publications] Hu、A.et al.: "Exposure of postnatal rats to glucocorticoids suppresses the development of choline acetyltransferase-immunoreactive neurons : role of adrenal steroids in the development of forebrain cholinergic neurons." J.Chem.Neuroanat.10. 1-10 (1996)

[Publications] Morimoto,M.et al.: "Phenotypic alterations of neuropeptide Y,vasoreactive interstinal peptide and cholone acetyltransferase in rat cultured cromaffin cells as effected by nerve growth factor and glucocorticoid." Arch.Histol.Cytol.59. 205-218 (1996)

[Publications] Ueda,S et al: "Altertion of serotonergic innervation in the suprachiasmatic nucleus of the rat following removal of input fibers from retina and lateral geniculatenucleus." Neurosci.Lett.211. 97-100 (1996)

[Publications] Yang, M.et al.: "The effects of nerve growth factor on newborn rat dosal root ganglion neurons in vitro." J.Brain Res.37. 313-317 (1996)

[Publications] Visser,D.T.M.et al.: "The alteration of glucocorticoid recepter-immunoreactivity in the rat forebrain following short-term and long-term adrenalectomy." Brain Res.729. 216-222 (1996)

[Publications] Ueda,S.et al: "Neuro-glial neurotrophic inteeraction in the S-100β retarded mutant mouse(Polydactyly Nagoya)." Brain Res.738. 15-23 (1996)

[Publications] Morimoto,M et al.: "Distribution of glucocorticoid receptor immunoreactivity and mRNA in the rat brain : an immunohistochemical and in situ hybridization study." Neurosci.Res. 26. 235-269 (1996)

[Publications] 堀哲郎et al.: "発熱の病体生理" Today's Therapy. 20. 115-118 (1996)

[Publications] Uchimura,D.: "Facilitatory effects of pituitary adenylate cyclase activating polypeptide(PACAP) on neurons in the magnocellular portion of the rat hypothalamic paraventricular nucleus(PVN) in vitro.21GC23:J.Neuroendocrinol" 8. 137-143 (1996)

[Publications] Li,A-J: "Fibroblast growth factor receptor-1 in the lateral hypothalamic area regulates food intake." Exptl.Neurol.137. 318-323 (1996)

[Publications] Shimizu,N: "Immoblization increases noradrenaline release and reduces NK cytotoxicity in spleen of conscious rat." Am.J.Physiol.271. R537-R544 (1996)

[Publications] Mo,Z.L.: "The effects of IL-1β on neuronal activities in the dorsal motor nucleus of the vagus in rat brain slices." Brain Res.Bull. 41. 249-255 (1996)

[Publications] Oka,T.: "Intracerebroventricular injection of tumor necrosis factor α induces thermal hyperalgesia in rats." Neuroimmunomodulation. 3. 135-140 (1996)

[Publications] Oka,T.: "Inhibition of peripheral interleukin-1-β-induced hyperalgesia by the intracerebroventricular administrationof diclofenac and α-melanocyte-stimulating horm one." Brain Res.736. 237-242 (1996)

[Publications] Oka,K: "The AV3V neurons which send axons to hypothalamic nuclei respond to the systemic injection of 1L-1β." Am.J.Physiol.(in press). (1997)

[Publications] Oka,T.: "Biphasic alteration in the trigeminal nociceptive neuronal responses after intracerebroventricular injection of prostaglandin E2 in rats." Brain Res.(in press). (1997)

[Publications] Li,A.J.: "Interleukin-6 inhibits long-term potentiation in rat hippocampal slices." Brain Res.(in press). (1997)

[Publications] Katafuchi,T.: "Differential effects of tumor necrosis factor-α and-β on the rat ventromedial hypothalamic neurons in vitro." Am.J.Physiol.(in press). (1997)

[Publications] 片渕俊彦: "交感神経による脾臓ナチュラルキラー細胞活性制御の視床下部機序" 自律神経. 33. 267-272 (1996)

[Publications] 岡孝和: "痛みと情動" Clinical Neuroscience. 14. 1025-1027 (1996)

[Publications] 河田光博et al.: "現代の神経内分泌学" 下垂体後葉ホルモンの産生、分布、分泌機能, 179-186 (1996)

[Publications] Hori,T.: "Discussion on Future Directions in Psychoneuroimmunology and Cancer." Nishimura Co.,Ltd.and Smith-Gordon Co.,Ltd., 166 (1996)

[Publications] Hori,T.: "Physiological Basis of Occupational Health : Stressful Environments." SPB Academic Publishing bv, 278 (1996)

[Publications] 堀哲郎: "現代の神経内分泌学" メディカル・サイエンス・インターナショナル, 506 (1996)

[Publications] 堀哲郎: "最新内科学大系、PartI.内科総論部門、第2巻「科学としての内科学」" 中山書店, 372 (1996)

山下博産業医科大学, 医学部, 教授 (00030841)