Chronic stress increases pituitary adenylate cyclase-activating peptide (PACAP) and brain-derived neurotrophic factor (BDNF) mRNA expression in the bed nucleus of the stria terminalis (BNST): roles for PACAP in anxiety-like behavior.
Chronic stress increases pituitary adenylate cyclase-activating peptide (PACAP) and brain-derived neurotrophic factor (BDNF) mRNA expression in the bed nucleus of the stria terminalis (BNST): roles for PACAP in anxiety-like behavior.
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DOI：
10.1016/j.psyneuen.2008.12.013
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发表时间：
2009-07
影响因子：
3.7
通讯作者：
May, Victor
中科院分区：
文献类型：
--
作者：
Hammack, Sayamwong E.;Cheung, Joseph;Rhodes, Kimberly M.;Schutz, Kristin C.;Falls, William A.;Braas, Karen M.;May, Victor
关键词：
暴露在慢性压力下会产生不适应的焦虑型行为状态，而与应激源反应相关的许多大脑区域也参与了焦虑型行为的调节。垂体腺苷环化酶激活多肽(PACAP)及其特异性的G蛋白偶联PAC1受体与许多应激和焦虑相关的脑区相关，通过这种肽能系统传递的信号可能促进与病理情感状态相关的神经可塑性。在这里，我们研究了慢性应激是否增加了几个核团中PACAP、PAC1受体、脑源性神经营养因子(BDNF)和酪氨酸受体激酶B(TrkB)的转录表达。在暴露于7天慢性变量应激范式的大鼠中，慢性应激增强了由处理和暴露在明亮灯光下引起的基线惊吓反应。慢性应激后，脑区定量转录评估显示，PACAP和PAC1受体、BDNF和TrkB受体mRNA选择性地在终纹前外侧床核(DBNST)的背侧表达显著增加。与对照组相比，相关的血管活性肠肽(VIP)和VPAC受体以及其他应激肽的转录水平没有改变。此外，将PACAP38急性注入dBNST导致了持续7天的基线惊吓反应的强健的剂量依赖的焦虑反应。PACAP/PAC1受体信号转导已经确立了营养功能，其与慢性应激诱导的dBNST、BDNF和TrkB转录表达的协同作用可能是与焦虑样行为相关的适应不良的BNST重塑和可塑性的基础。
Exposure to chronic stress has been argued to produce maladaptive anxiety-like behavioral states, and many of the brain regions associated with stressor responding also mediate anxiety-like behavior. Pituitary adenylate cyclase activating polypeptide (PACAP) and its specific G protein-coupled PAC1 receptor have been associated with many of these stress- and anxiety-associated brain regions, and signaling via this peptidergic system may facilitate the neuroplasticity associated with pathological affective states. Here we investigated whether chronic stress increased transcript expression for PACAP, PAC1 receptor, brain-derived neurotrophic factor (BDNF), and tyrosine receptor kinase B (TrkB) in several nuclei. In rats exposed to a 7 day chronic variate stress paradigm, chronic stress enhanced baseline startle responding induced by handling and exposure to bright lights. Following chronic stress, quantitative transcript assessments of brain regions demonstrated dramatic increases in PACAP and PAC1 receptor, BDNF, and TrkB receptor mRNA expression selectively in the dorsal aspect of the anterolateral bed nucleus of the stria terminalis (dBNST). Related vasoactive intestinal peptide (VIP) and VPAC receptor, and other stress peptide transcript levels were not altered compared to controls. Moreover, acute PACAP38 infusion into the dBNST resulted in a robust dose-dependent anxiogenic response on baseline startle responding that persisted for 7 days. PACAP/PAC1 receptor signaling has established trophic functions and its coordinate effects with chronic stress-induced dBNST BDNF and TrkB transcript expression may underlie the maladaptive BNST remodeling and plasticity associated with anxiety-like behavior.
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DOI：
10.1016/s0165-3806(99)00192-3
发表时间：
2000-03-15
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Jaworski, DM;Proctor, MD
通讯作者：
Proctor, MD
影响因子：
4.7
作者：
Girard, Beatrice A.;Lelievre, Vincent;May, Victor
通讯作者：
May, Victor
影响因子：
--
作者：
Norrholm, SD;Das, M;Légrádi, G
通讯作者：
Légrádi, G
影响因子：
2.9
作者：
Kozicz, T;Vigh, S;Arimura, A
通讯作者：
Arimura, A
影响因子：
1.9
作者：
Hammack, SE;Richey, KJ;Maier, SF
通讯作者：
Maier, SF