Analysis of brain-heart interaction in response to emotional stress using animal model of psychosomatic disease

使用心身疾病动物模型分析脑心相互作用对情绪应激的反应

• 批准号: 15590603
• 负责人: UEYAMA Takashi
• 金额: $ 2.24万
• 依托单位: Wakayama Medical University, School of medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590603/
• 关键词: stress; model animal; acute heart failure; estrogen; psychosomatic disease; gene expression; neuroscience; catecholamine; たこつぼ型心筋症; 動物モデル; 心臓; 脳; 情動的ストレス; 交感神経

Emotional or physical stress triggers Tako-tsubo cardiomyopathy in postmenopausal female, which is characterized by elevation of ST segment in the ECG and left ventricular apical ballooning in the LVG. We succeeded to mimic this cardiac attack using immobilization stress (IMO) of rats, a well-known animal model of emotional stress. IMO-induced cardiac changes are completely cancelled by pretreatment with combined blockade of α- and β-adrenoceptors, suggesting that exaggerated sympatho-adrenomedullary outflow is involved in the cardiac change. To study whether these cardiac changes are especially predominant in elderly female subjects, we compared cardiac function and the induction of c-fos mRNA or c-Fos- immunoreactive(IR) in the heart or the brain in response to IMO between ovariectomized rats with placebo treatment (OVX+P) and ovariectomized rats supplemented with b-estradiol (OVX+E).1.In OVX+P rats, % contraction in LVG was significantly reduced in response to stress, whole it was n … More ot significantly changed in OVX+E rats. In both groups, heart rate was significantly increased in response to stress. However, heart rate in stress was significantly higher in OVX+P than in OVX+E.2.Expression of c-fos mRNA in the heart and paraventricular hypothalamic nucleus in response to IMO was attenuated in OVX+E.3.Innervation of catechoraminergic nerve fibers was reduced in OVX+E.4.Increased c-Fos-IR cells in response to IMO were observed in cerebral cortex, septum, thalamus, hypothalamus, midbrain, pons and medulla oblongata in accordance with previous findings. In OVX+E compared with OVX+P, the numbers of c-Fos-IR cells were significantly lower in the lateral septum, paraventricular hypothalamic nucleus, dorsomedial hypothalamic nucleus, medial amygdaloid nucleus, lateral periaqueductal gray, laterodorsal, tegmental nucleus and locus coeruleus, while they were significantly higher in paraventricular thalamic nucleus and nucleus of the solitary tract. These data suggest that neuronal activity in these areas is influenced by systemic estrogen level.Taken together, estrogen attenuates the stress response in the central nervous system and cardiac tissues. In turn, reduction of estrogen may underline the high incidence of stress-induced Tako-tsubo carrdiomyopathy in postmenoausal female. Less

精神或身体应激诱发绝经后女性Tako-tsubo心肌病，其特征为心电图ST段抬高和左室心尖部气球样变。我们成功地模拟了这种心脏病发作，使用固定应激（IMO）的大鼠，一个众所周知的动物模型的情绪压力。联合阻断α-和β-肾上腺素能受体可完全消除IM O诱导的心脏变化，表明交感-肾上腺髓质流出增加参与了心脏变化。为了研究这些心脏变化是否在老年女性受试者中特别突出，我们比较了安慰剂治疗的去卵巢大鼠（OVX+P）和补充b-雌二醇的去卵巢大鼠（OVX+E）对IMO的心功能和心或脑中c-fos mRNA或c-Fos免疫反应性（IR）的诱导。LVG的收缩%在应激反应中显著降低，总体上为n ...更多信息 OVX+E组则无明显变化。在这两组中，心率在应激反应中显著增加。OVX + E组大鼠心脏和室旁核c-fos mRNA的表达明显减弱，儿茶酚胺能神经纤维的支配减少。脑桥和延髓与以前的结果一致。与OVX+P组相比，OVX+E组大鼠外侧隔、下丘脑室旁核、背内侧核、杏仁内侧核、外侧导水管周围灰质、背外侧核、被盖核和蓝斑的c-Fos-IR细胞数明显减少，而下丘脑室旁核和孤束核的c-Fos-IR细胞数明显增加。这些数据表明，这些区域的神经元活动受到全身雌激素水平的影响。综上所述，雌激素减弱了中枢神经系统和心脏组织的应激反应。反过来，雌激素的减少可能强调了绝经后女性应激诱导的Tako-tsubo心肌病的高发病率。少

项目成果

上山敬司 他: "「たこつぼ型心筋症」モデル動物の作製とエストロゲンの関与"自律神経. 40. 350-353 (2003)

Keiji Ueyama 等人：“Takotsubo 心肌病动物模型的创建和雌激素的参与”《自主神经系统》40. 350-353 (2003)。

No Involvement of NGF Gene Locus in Hypertension in Spontaneously Hypertensive Rats.

NGF 基因位点与自发性高血压大鼠的高血压无关。

• 发表时间: 2005
• 期刊: Hypertens Res 28
• 作者: 上山敬司 他;Nemoto K et al.
• 通讯作者: Nemoto K et al.

STAT6 deficiency inhibits tubulointerstitial fibrosis in obstructive nephropathy

STAT6 缺陷抑制梗阻性肾病的肾小管间质纤维化

• 发表时间: 2005
• 期刊: Int J Mol Med 15
• 作者: 上山敬司 他;Nemoto K et al.;Nemoto K;Yukawa K;Yukawa K;Yukawa K et al.;Yukawa K et al.
• 通讯作者: Yukawa K et al.

Molecular mechanism of emotional stress- and catecholamine-induced heart attack.

情绪压力和儿茶酚胺诱发心脏病的分子机制。

• 发表时间: 2003
• 期刊: J Cardiovasc Pharmacol 41 Suppl 1
• 作者: Tsuruo Y;Yokoi H;Tsuruo Y;Yokoi H;Tsuruo Y;Ueyama T;Shirasawa N;Yukawa K;Morita K;Shirasawa N;Morita K;Yukawa N;Ueyama T
• 通讯作者: Ueyama T

Emotional Stress-induced Tako-tsubo Cardiomyopathy-Animal model and Molecular Mechanism P437-444- Stress : Current Neuroendocrine and Generic Approaches Ann NY Acad Sci Vol1010 (Edited by Karel Pacak, Gretti Aguilera, Ester Sabban, and Richard Kvetnansky)

情绪压力诱发的 Tako-tsubo 心肌病 - 动物模型和分子机制 P437-444 - 压力：当前神经内分泌和通用方法 Ann NY Acad Sci Vol1010（由 Karel Pacak、Gretti Aguilera、Ester Sabban 和 Richard Kvetnansky 编辑）

• 发表时间: 2004
• 作者: 上山敬司 他;Nemoto K et al.;Nemoto K;Yukawa K;Yukawa K;Yukawa K et al.;Yukawa K et al.;Nemoto K et al.;Kuzumoto N et al.;Ueyama T et al.;Ueyama T;Ueyama T;Kuzumoto N;Ueyama T et al.;Ueyama T;Kuzumoto N et al.;上山 敬司;Ueyama T;Ueyama T;Ueyama T;Ueyama T
• 通讯作者: Ueyama T