摘要

Chronic stress is a major cause of anxiety disorders that can be reliably modeled preclinically, providing insight into alternative therapeutic targets for this mental health illness. Neuropeptides have been targeted in the past to no avail possibly due to our lack of understanding of their role in pathological models. In this study we use a rat model of chronic stress-induced anxiety-like behaviors and hypothesized that neuropeptidergic modulation of synaptic transmission would be altered in the bed nucleus of the stria terminalis (BNST), a brain region suspected to contribute to anxiety disorders. We use brain slice neurophysiology and behavioral pharmacology to compare the role of locally released endogenous neuropeptides on synaptic transmission in the oval (ov) BNST of non-stressed (NS) or chronic unpredictably stressed (CUS) rats. We found that in NS rats, post-synaptic depolarization induced the release of vesicular neurotensin (NT) and corticotropin-releasing factor (CRF) that co-acted to increase ovBNST inhibitory synaptic transmission in 59% of recorded neurons. CUS bolstered this potentiation (100% of recorded neurons) through an enhanced contribution of NT over CRF. In contrast, locally released opioid neuropeptides decreased ovBNST excitatory synaptic transmission in all recorded neurons, regardless of stress. Consistent with CUS-induced enhanced modulatory effects of NT, blockade of ovBNST NT receptors completely abolished stress-induced anxiety-like behaviors in the elevated plus maze paradigm. The role of NT has been largely unexplored in stress and our findings highlight its potential contribution to an important behavioral consequence of chronic stress, that is, exaggerated avoidance of open space in rats.

译文

慢性压力是焦虑症的主要原因,可以在临床前进行可靠的建模,为这种精神健康疾病的替代治疗目标提供见解。神经肽在过去已经被靶向,但可能由于我们缺乏对其在病理模型中的作用的理解而无济于事。在本研究中,我们使用了一个慢性应激诱导的焦虑样行为的大鼠模型,并假设突触传递的神经肽类调节会在终末纹床核 (BNST) 中改变, 被怀疑导致焦虑症的大脑区域。我们使用脑切片神经生理学和行为药理学来比较局部释放的内源性神经肽对非应激 (NS) 的椭圆形 (ov) BNST 突触传递的作用或者慢性不可预测压力 (CUS) 大鼠。我们发现在 NS 大鼠中,突触后去极化诱导囊泡神经降压素 (NT) 和促肾上腺皮质激素释放因子 (CRF) 的释放。这一共同作用增加了 59% 记录神经元的 ovBNST 抑制性突触传递。CUS 通过 NT 对 CRF 的增强贡献支持了这种增强作用 (100% 的记录神经元)。相比之下,局部释放的阿片类神经肽降低了所有记录神经元的 ovBNST 兴奋性突触传递,而不管压力如何。与 CUS 诱导的 NT 增强调节效应一致,在高架十字迷宫范式中,对 ovBNST NT 受体的阻断完全消除了应激诱导的焦虑样行为。NT 在压力中的作用在很大程度上尚未被探索,我们的发现强调了它对慢性压力的一个重要行为后果的潜在贡献,即大鼠对开放空间的过度回避。

Neurotensin

神经 肽类激素 临床研究术语
概述  :  

神经降压肽(NT)是广泛分布于胃肠道的肽类激素,具有广泛的生物学功能。现已确定NT是一种含13个氨基酸残基的单键多肽,其氨基端为一个环状的Gin,羧基端是游离的,也时其受体结合部位所在。NT的生物活性主要取决于C端。NT广泛分布与脑和胃肠道中,85%在肠道,是由肠道N细胞分泌的,少量由肠道肌间神经从的神经纤维产生。N细胞主要分布于末端回肠黏膜内,空肠次之,胃、十二指肠和结肠含量很少。N细胞有一突起伸向肠黏膜刷状缘,与肠腔相通。因此,N细胞属于肠道开放型内分泌细胞。分布中枢神经系统:NT在中枢

neurotensin

释    义   n. [生化] 神经降压素

短    语   neurotensin receptor 神经降压素受体

neurotensin assay 神经降压素测定

例    句   Our findings suggest that curcumin may be useful for colon cancer treatment, as well as potentialcolon cancer suppression, in cells that respond to this gastrointestinal hormone, neurotensin. 我们的发现表明黄素可能对治疗结肠癌很有用,同时在对胃肠激素神经降压素起反应的细胞内对结肠癌有潜在的抑制作用。

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