1997 Fiscal Year Annual Research Report

遺伝子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
Research Institution	University of Occupational and Environmental Health
Principal Investigator	山下博産業医科大学, 医学部, 教授 (00030841)
Co-Investigator(Kenkyū-buntansha)	稲永清敏九州歯科大学, 歯学部, 教授 (90131903) 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 / 唾液腺 / 味覚神経 / 侵害受容行動 / 胸腺 / グルココルチコイド受容体 / バゾプレッシン / 学習行動解析
Research Abstract	本研究は遺伝性多飲マウスの高次機能から遺伝子レべルにわたる解析を行ない、種々の環境ストレスに対する神経・内分泌・免疫系応答やその関連異常のメカニズムに迫り、最終的にはこのストレインを用いて環境ストレス応答モデル動物を碓立することを目的としている。遭伝性多飲マウスでは、1.ピロカルピン刺激による唾液分泌および唾液腺血流の増加反応が見られず、ムスカリン受容体の異常が示唆された。2.味覚神経の反応性を検討するために、上喉頭神経の神経活動を記録したところ、自発放電が少なく、高濃度の食塩水刺激に大きな応答を示した。3.侵害受容行動を検討したところ、ホットプレートテストにおいて痛覚閾値が低下していた。その機序としてオピオイド受容体の減少によることが示唆された。4.免疫能を検討したところ、胸腺細胞数が増加しているがインターロイキン1βに対する反応性が低下しており、T細胞の分化異常が示唆された。5.副腎皮質ホルモンであるグルココルチコイドの受容体の脳内分布を検討したところ室傍核、脳弓下器官、扁桃体、海馬で強い発現が見られた。6.脳内でのNO産生およびNO合成酵素の分布を検討したところ、室傍核で増加していたが、下垂体で減少しており、今後の検討が必要である。7.多尿発症時期である8週令前後での遺伝性多飲マウスの視索上核バゾプレッシンmRNAの発現量は、多尿発症時期で減少、発症後では増加していた。下垂体のバゾプレッシン含有量は多尿発症前後で差はなかった。8.学習行動解析を行なったところ、受動回避テストでは回避率及び回避時間に異常が見られ、モ-リス水迷路テストではいつまでも憶えないものがいた。上記のように、遺伝性多飲マウスには種々の異常が見られ、環境ストレス応答モデル動物として有用であることが示唆された。

Research Products

(30 results)

All Other

All Publications (30 results)

[Publications] Shimizu,K., et al.: "Selective expression of HSP70-1 gene in the adrenal cortex but not in the medull of themally stressed rats" Biochem.Biophys.Res.Commun.233. 550-554 (1997)
[Publications] Inenaga,K., et al.: "Osmotic modullation in glutamatergic excitatory synaptic tnpucts toneurons in the supraoptic nucleus of rat hypothalamus in vitro" J.Neuroendocrinol.9. 63-68 (1997)
[Publications] Shibuya, I., et al.: "Both GABA_A and GABA_B neceptors participate in suppression of [Ca^<2+>],pulsing in toad melanorcophs" Eur.J.Pharmacol.321. 241-246 (1997)
[Publications] Yamamoto,S., et al.: "Parathyroid hormone-related peptide-(1-34)[PTHrP-(1-34)]induces vasopressin release from the rat supraoptic nucleus in vitro throuyh a novel receptor distinct from a type I a type PTH/PTHrP recepeor" Endocrinology. 138. 2066-2072 (1997)
[Publications] Hara,Y., et al.: "Increase of urocortin-like immunoreactivity in the hypothalamuo-neuvolypophysial system afterisalt loading and hypognysedomry" Neurosci.Lett.227. 127-130 (1997)
[Publications] Yamamoto,S., et al.: "C-type natriuretic peptide suppresses arginine-vasopressin secretion from dissaiated magnacllular neurons in newborn rat supraopic nucleus" Neurosci.Lett.229. 97-100 (1997)
[Publications] Tokunaga,M., et al.: "PTH-related peptide-like immunoreactivity in the wedian emineuce,paraventriculay and supraoptic nuclei in colhicine-terated rates." Brain Rse.774. 216-220 (1997)
[Publications] Uezono,Y., et al.: "Enhancement by baclofen of Gs-coupled receptor receptor mediated cAMP production in xenopus oocytes expressory rat brain cortex poly(A)^+ RNA:A role of G-protein Br subun" Biochem.Biophys.Res.Commun.241. 476-480 (1997)
[Publications] Yamamoto,S., et al.: "Centrally administered paruthyroid hormone(PTH)-related protein (1-34)but not PTH(1-34)shimulates arginine vasopressin and its messenger ribonudeic acid expression in supoaoptic nucleus of the cohscious rats" Endocrinology. 139. 383-388 (1998)
[Publications] Shibuya,I., et al.: "PACAP increaes the cytosolic Ca^<2+> concentration and stimulates somatodendritic[vasopressin release in rat supraoptic neurons" J.Neuroendocrinol.10. 31-42 (1998)
[Publications] Ueta,Y., et al.: "Neuronal nitric oxied synthase gene expression in human pituitury tumars a possible association with somatotron adenolnas and gronlth hormone-reieasug hormone gene expression" Clin.Endocrnol.(in press).
[Publications] Tanaka,K., et al.: "PACAP causes Ca^<2+> release from ryanodine/caffeine stores through a novel pathway independent of both IP_3 and cAMP in bovine adrenal medullary cells" J.Neurochem.(in press).
[Publications] Hara,Y., et al.: "Increase of urowotin-like immucro reactivity in the rat supraoptic nucleus after dehydration but not food deprivation" Neurosci.Lett.229. 65-68 (1997)
[Publications] Anai,H., et al.: "Upregulation of the expression of vasopression gene in the paraventricular and supraoptic nuclei of the lithium-induced diabetes insipidus rat" Brain Res.772. 161-166 (1997)
[Publications] Tanaka,K., et al.: "Pituitary adenylate cyclase-activating polypeptide poteutiation of Ca^<2+> entry via protein kinase C and A pathways in melanotrophs of the pituitany pars intermedia of rat" Endocrinology. 138. 4086-4095 (1997)
[Publications] Nomura,M., et al.: "Water deprivation incveases the expression of pituitary adenylatecyclaseactivating polypeptide gene in the rat subfornical organ" Endocrinology. 138. 4096-4100 (1997)
[Publications] Kabashima,N., et al.: "Inhibition of spontaneovs EPSCsand IPSCs by presynaptic GABA_B receptors on rat snpraoptic magnocellular neurons" J.Physiol.(Lond.). 504. 113-126 (1997)
[Publications] Yamamoto,Y., et al.: "Upregulation of neuronal NOSmRNA in the PVN and SON of inherited diabetes insipidus rats" NeuroReport. 8. 3907-3911 (1997)
[Publications] Ueta,Y., et al.: "Hypovolemia upregulates the expression of neuronal nitric oxide synthase gene in the paraventrcular and supraopric nuclei of rats" Brain Rse.(in press).
[Publications] Hattori,Y., et al.: "Ionotrophic and metabotropic glutamate recepta agonist-induced [Ca^<2+>];increase in isolated rat supraoptic neurones" J.Neuraeudocrinol.(in press).
[Publications] Asada,N., et al.: "Ideutification of α and β cellsin intact isolated islet of Langerhans by their characteristic [Ca^<2+>]c dynamocs and immunocytochewical staining" Diabetes. (in press).
[Publications] Uezono,Y., et al.: "Adrenomedullin increases intracellular Ca^<2+> and inosifol 1,4,S-triphosphate in human oligodendroglial cell line KG-lC." Brain Res.(in press).
[Publications] Uezono,Y., et al.: "Activation of inwardly rectifying K^+ by GABA-B receptors expresses in Xenopud ooztes" NeuroReport. (in press).
[Publications] Harayama,N., et al.: "Inhibition of N-and P/Q-type calcium channels by postsynaphc GABA_B receptor activation in rat supraoptic renrones" J.Physiol,(Lond.). (in press).
[Publications] Serino,R., et al.: "Upregulation of hypothalgmic nitric oxide synthase gene expression in streptozotocin-induced diabetic rats" Diabetologia. (in press).
[Publications] Shibuya,I., et al.: "The Adrenal Chromaffin Cell" Hokkaido Llniv.Press, (1997)
[Publications] Yamashita,H.: "The ethics of life" UNESCO, 238 (1997)
[Publications] 山下博, 他: "循環器科" 科学評論社, (1997)
[Publications] 澁谷泉, 他: "内分泌・糖尿病科" 科学評論社,
[Publications] 上田陽一, 他: "医学のあゆみ" 医歯薬出版, 102 (1998)

1997 Fiscal Year Annual Research Report

遺伝子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] Shimizu,K., et al.: "Selective expression of HSP70-1 gene in the adrenal cortex but not in the medull of themally stressed rats" Biochem.Biophys.Res.Commun.233. 550-554 (1997)

[Publications] Inenaga,K., et al.: "Osmotic modullation in glutamatergic excitatory synaptic tnpucts toneurons in the supraoptic nucleus of rat hypothalamus in vitro" J.Neuroendocrinol.9. 63-68 (1997)

[Publications] Shibuya, I., et al.: "Both GABA_A and GABA_B neceptors participate in suppression of [Ca^<2+>],pulsing in toad melanorcophs" Eur.J.Pharmacol.321. 241-246 (1997)

[Publications] Yamamoto,S., et al.: "Parathyroid hormone-related peptide-(1-34)[PTHrP-(1-34)]induces vasopressin release from the rat supraoptic nucleus in vitro throuyh a novel receptor distinct from a type I a type PTH/PTHrP recepeor" Endocrinology. 138. 2066-2072 (1997)

[Publications] Hara,Y., et al.: "Increase of urocortin-like immunoreactivity in the hypothalamuo-neuvolypophysial system afterisalt loading and hypognysedomry" Neurosci.Lett.227. 127-130 (1997)

[Publications] Yamamoto,S., et al.: "C-type natriuretic peptide suppresses arginine-vasopressin secretion from dissaiated magnacllular neurons in newborn rat supraopic nucleus" Neurosci.Lett.229. 97-100 (1997)

[Publications] Tokunaga,M., et al.: "PTH-related peptide-like immunoreactivity in the wedian emineuce,paraventriculay and supraoptic nuclei in colhicine-terated rates." Brain Rse.774. 216-220 (1997)

[Publications] Uezono,Y., et al.: "Enhancement by baclofen of Gs-coupled receptor receptor mediated cAMP production in xenopus oocytes expressory rat brain cortex poly(A)^+ RNA:A role of G-protein Br subun" Biochem.Biophys.Res.Commun.241. 476-480 (1997)

[Publications] Yamamoto,S., et al.: "Centrally administered paruthyroid hormone(PTH)-related protein (1-34)but not PTH(1-34)shimulates arginine vasopressin and its messenger ribonudeic acid expression in supoaoptic nucleus of the cohscious rats" Endocrinology. 139. 383-388 (1998)

[Publications] Shibuya,I., et al.: "PACAP increaes the cytosolic Ca^<2+> concentration and stimulates somatodendritic[vasopressin release in rat supraoptic neurons" J.Neuroendocrinol.10. 31-42 (1998)

[Publications] Ueta,Y., et al.: "Neuronal nitric oxied synthase gene expression in human pituitury tumars a possible association with somatotron adenolnas and gronlth hormone-reieasug hormone gene expression" Clin.Endocrnol.(in press).

[Publications] Tanaka,K., et al.: "PACAP causes Ca^<2+> release from ryanodine/caffeine stores through a novel pathway independent of both IP_3 and cAMP in bovine adrenal medullary cells" J.Neurochem.(in press).

[Publications] Hara,Y., et al.: "Increase of urowotin-like immucro reactivity in the rat supraoptic nucleus after dehydration but not food deprivation" Neurosci.Lett.229. 65-68 (1997)

[Publications] Anai,H., et al.: "Upregulation of the expression of vasopression gene in the paraventricular and supraoptic nuclei of the lithium-induced diabetes insipidus rat" Brain Res.772. 161-166 (1997)

[Publications] Tanaka,K., et al.: "Pituitary adenylate cyclase-activating polypeptide poteutiation of Ca^<2+> entry via protein kinase C and A pathways in melanotrophs of the pituitany pars intermedia of rat" Endocrinology. 138. 4086-4095 (1997)

[Publications] Nomura,M., et al.: "Water deprivation incveases the expression of pituitary adenylatecyclaseactivating polypeptide gene in the rat subfornical organ" Endocrinology. 138. 4096-4100 (1997)

[Publications] Kabashima,N., et al.: "Inhibition of spontaneovs EPSCsand IPSCs by presynaptic GABA_B receptors on rat snpraoptic magnocellular neurons" J.Physiol.(Lond.). 504. 113-126 (1997)

[Publications] Yamamoto,Y., et al.: "Upregulation of neuronal NOSmRNA in the PVN and SON of inherited diabetes insipidus rats" NeuroReport. 8. 3907-3911 (1997)

[Publications] Ueta,Y., et al.: "Hypovolemia upregulates the expression of neuronal nitric oxide synthase gene in the paraventrcular and supraopric nuclei of rats" Brain Rse.(in press).

[Publications] Hattori,Y., et al.: "Ionotrophic and metabotropic glutamate recepta agonist-induced [Ca^<2+>];increase in isolated rat supraoptic neurones" J.Neuraeudocrinol.(in press).

[Publications] Asada,N., et al.: "Ideutification of α and β cellsin intact isolated islet of Langerhans by their characteristic [Ca^<2+>]c dynamocs and immunocytochewical staining" Diabetes. (in press).

[Publications] Uezono,Y., et al.: "Adrenomedullin increases intracellular Ca^<2+> and inosifol 1,4,S-triphosphate in human oligodendroglial cell line KG-lC." Brain Res.(in press).

[Publications] Uezono,Y., et al.: "Activation of inwardly rectifying K^+ by GABA-B receptors expresses in Xenopud ooztes" NeuroReport. (in press).

[Publications] Harayama,N., et al.: "Inhibition of N-and P/Q-type calcium channels by postsynaphc GABA_B receptor activation in rat supraoptic renrones" J.Physiol,(Lond.). (in press).

[Publications] Serino,R., et al.: "Upregulation of hypothalgmic nitric oxide synthase gene expression in streptozotocin-induced diabetic rats" Diabetologia. (in press).

[Publications] Shibuya,I., et al.: "The Adrenal Chromaffin Cell" Hokkaido Llniv.Press, (1997)

[Publications] Yamashita,H.: "The ethics of life" UNESCO, 238 (1997)

[Publications] 山下 博, 他: "循環器科" 科学評論社, (1997)

[Publications] 澁谷 泉, 他: "内分泌・糖尿病科" 科学評論社,

[Publications] 上田陽一, 他: "医学のあゆみ" 医歯薬出版, 102 (1998)

山下博産業医科大学, 医学部, 教授 (00030841)

[Publications] 山下博, 他: "循環器科" 科学評論社, (1997)

[Publications] 澁谷泉, 他: "内分泌・糖尿病科" 科学評論社,