The CRF Family of Neuropeptides and their Receptors - Mediators of the Central Stress Response.
The CRF Family of Neuropeptides and their Receptors - Mediators of the Central Stress Response.
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DOI：
10.2174/1874467210666170302104053
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发表时间：
2018
影响因子：
2.7
通讯作者：
Deussing JM
中科院分区：
文献类型：
--
作者：
Dedic N;Chen A;Deussing JM
由遗传和/或环境变化引起的应激神经回路失调是许多神经精神疾病发展的基础。促肾上腺皮质激素释放因子（Corticotropin-releasing factor，CRF）是下丘脑-垂体-肾上腺（hypothalamic-pituitary-adrenal，HPA）轴的主要生理激活因子，是哺乳动物应激反应的主要调节因子。与其三个家族成员尿皮质素（UCN）1，2和3一起，CRF通过激活其同源受体CRFR 1和CRFR 2整合了神经内分泌，自主神经，代谢和行为对应激的反应。 本文综述了CRF/CRFR领域的过去和现状，从药理学研究到遗传小鼠模型和病毒介导的操作。 尽管CRF/CRFR 1信号传导介导了包括焦虑和抑郁样行为在内的厌恶反应，但最近的一些研究通过揭示特定CRF/CRFR 1回路的抗焦虑和食欲特性来挑战这一观点。相比之下，UCN/CRFR 2系统的了解较少，可能也发挥不同的功能，生理和行为取决于大脑区域，底层电路，和/或经历的压力条件。 大量可用的遗传工具，包括针对CRF系统组分的常规和条件性小鼠突变体，极大地推进了我们对HPA系统调节的内源性机制和参与应激相关行为的CRF/UCN相关神经元回路的理解。然而，CRF/UCN系统将负性或正性刺激转化为最终的、整合的生物反应的详细途径和分子机制尚未完全了解。利用未来的补充方法，如细胞类型特异性Cre-driver线，病毒和光遗传学工具，将有助于进一步剖析基因定义的CRF/UCN神经回路在适应性和适应不良应激反应的背景下的功能。
Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is the major physiological activator of the hypothalamic-pituitary-adrenal (HPA) axis and conse-quently a primary regulator of the mammalian stress response. Together with its three family members, urocortins (UCNs) 1, 2, and 3, CRF integrates the neuroendocrine, autonomic, metabolic and behavioral responses to stress by activating its cognate receptors CRFR1 and CRFR2. Here we review the past and current state of the CRF/CRFR field, ranging from pharmacologi-cal studies to genetic mouse models and virus-mediated manipulations. Although it is well established that CRF/CRFR1 signaling mediates aversive responses, includ-ing anxiety and depression-like behaviors, a number of recent studies have challenged this viewpoint by revealing anxiolytic and appetitive properties of specific CRF/CRFR1 circuits. In contrast, the UCN/CRFR2 system is less well understood and may possibly also exert divergent functions on physiol-ogy and behavior depending on the brain region, underlying circuit, and/or experienced stress conditions. A plethora of available genetic tools, including conventional and conditional mouse mutants targeting CRF system components, has greatly advanced our understanding about the endogenous mecha-nisms underlying HPA system regulation and CRF/UCN-related neuronal circuits involved in stress-related behaviors. Yet, the detailed pathways and molecular mechanisms by which the CRF/UCN-system translates negative or positive stimuli into the final, integrated biological response are not completely un-derstood. The utilization of future complementary methodologies, such as cell-type specific Cre-driver lines, viral and optogenetic tools will help to further dissect the function of genetically defined CRF/UCN neurocircuits in the context of adaptive and maladaptive stress responses.
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DOI：
10.1523/jneurosci.1393-11.2011
发表时间：
2011-08-03
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Blacktop JM;Seubert C;Baker DA;Ferda N;Lee G;Graf EN;Mantsch JR
通讯作者：
Mantsch JR
影响因子：
3.4
作者：
Boyson, Christopher O.;Miguel, Tarciso T.;Quadros, Isabel M.;DeBold, Joseph F.;Miczek, Klaus A.
通讯作者：
Miczek, Klaus A.
影响因子：
4.8
作者：
Bale, TL;Anderson, KR;Vale, WW
通讯作者：
Vale, WW
影响因子：
25
作者：
Boyden, ES;Zhang, F;Deisseroth, K
通讯作者：
Deisseroth, K
影响因子：
4.8
作者：
Bentley L;Esapa CT;Nesbit MA;Head RA;Evans H;Lath D;Scudamore CL;Hough TA;Podrini C;Hannan FM;Fraser WD;Croucher PI;Brown MA;Brown SD;Cox RD;Thakker RV
通讯作者：
Thakker RV