A key role for orexin in panic anxiety.
A key role for orexin in panic anxiety.
复制标题
DOI：
10.1038/nm.2075
复制
发表时间：
2010-01
期刊：
影响因子：
82.9
通讯作者：
Shekhar, Anantha
中科院分区：
文献类型：
--
作者：
Johnson, Philip L.;Truitt, William;Fitz, Stephanie D.;Minick, Pamela E.;Dietrich, Amy;Sanghani, Sonal;Traskman-Bendz, Lil;Goddard, Andrew W.;Brundin, Lena;Shekhar, Anantha
恐慌症是一种严重的焦虑症，具有反复发作的，使人衰弱的恐慌发作。在惊恐障碍受试者中，有证据表明，静脉输注0.5 M乳酸钠后，中枢GABA能活性降低，自主神经和呼吸反应显著增加。在惊恐障碍的动物模型中，大鼠背内侧/穹窿周围下丘脑中GABA合成的慢性抑制产生焦虑样状态和对乳酸钠诱导的心脏兴奋性反应的类似脆弱性。背内侧/穹窿周围下丘脑富含含食欲素（ORX，也称为下丘脑泌素）的神经元，这些神经元在唤醒、警惕和中枢自主神经动员中起着关键作用，所有这些都是恐慌的关键组成部分。在这里，我们证明了ORX神经元的激活是必要的发展恐慌倾向的状态，在动物模型中，无论是沉默下丘脑ORX基因（Hcrt）产品与RNA干扰或全身ORX 1拮抗剂块恐慌反应。此外，我们发现，与没有恐慌焦虑的受试者相比，恐慌焦虑的受试者脑脊液中ORX水平升高。综上所述，我们的研究结果表明，ORX系统可能参与了惊恐性焦虑的病理生理学，ORX拮抗剂构成了一种潜在的新的治疗惊恐障碍的策略。
Panic disorder is a severe anxiety disorder with recurrent, debilitating panic attacks. In subjects with panic disorder there is evidence of decreased central GABAergic activity as well as marked increases in autonomic and respiratory responses following intravenous infusions of 0.5M sodium lactate. In an animal model of panic disorder, chronic inhibition of GABA synthesis in the dorsomedial/perifornical hypothalamus of rats produces anxiety-like states and a similar vulnerability to sodium lactate-induced cardioexcitatory responses. The dorsomedial/perifornical hypothalamus is enriched in orexin (ORX, also known as hypocretin)-containing neurons that play a critical role in arousal, vigilance and central autonomic mobilization, all of which are key components of panic. Here, we demonstrate that activation of the ORX neurons is necessary for developing a panic-prone state in the animal model, and either silencing the hypothalamic ORX gene (Hcrt) product with RNA interference or systemic ORX1 antagonists blocks the panic responses. Moreover, we show that subjects with panic anxiety have elevated levels of ORX in the cerebrospinal fluid compared to subjects without panic anxiety. Taken together our results suggest that the ORX system may be involved in the pathophysiology of panic anxiety, and that ORX antagonists constitute a potential novel treatment strategy for panic disorder.
登录
查看更多内容
DOI：
10.1590/s0100-879x2001000200001
发表时间：
2001-02-01
影响因子：
2.3
作者：
Andreatini, R;Blanchard, C;Graeff, FG
通讯作者：
Graeff, FG
影响因子：
7.4
作者：
Ludewig, S;Ludewig, K;Vollenweider, FX
通讯作者：
Vollenweider, FX
影响因子：
10.6
作者：
COWLEY, DS;DAGER, SR;DUNNER, DL
通讯作者：
DUNNER, DL
影响因子：
56.9
作者：
Rupprecht, Rainer;Rammes, Gerhard;Kucher, Klaus
通讯作者：
Kucher, Klaus
影响因子：
82.9
作者：
Brisbare-Roch, Catherine;Dingemanse, Jasper;Jenck, Francois
通讯作者：
Jenck, Francois