Striatal-enriched protein tyrosine phosphatase-STEPs toward understanding chronic stress-induced activation of corticotrophin releasing factor neurons in the rat bed nucleus of the stria terminalis.
Striatal-enriched protein tyrosine phosphatase-STEPs toward understanding chronic stress-induced activation of corticotrophin releasing factor neurons in the rat bed nucleus of the stria terminalis.
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DOI：
10.1016/j.biopsych.2013.07.032
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发表时间：
2013-12-01
影响因子：
10.6
通讯作者：
Rainnie, Donald G.
中科院分区：
文献类型：
--
作者：
Dabrowska, Joanna;Hazra, Rimi;Guo, Ji-Dong;Li, ChenChen;DeWitt, Sarah;Xu, Jian;Lombroso, Paul J.;Rainnie, Donald G.
关键词：
STEP是一种脑特异性蛋白酪氨酸磷酸酶，它可以阻止突触强化和恐惧记忆的巩固。相反，压力促进恐惧记忆的形成，可能是通过激活终纹床核（BNSTALG）前外侧细胞群中的促肾上腺皮质激素释放因子（CRF）神经元。在这里，使用双重免疫荧光，单细胞RT-PCR，定量RT-PCR，Western印迹，和全细胞膜片钳电生理学，我们研究了STEP的表达和作用，在调节大鼠BNSTALG神经元的突触可塑性，其调制的压力。STEP选择性表达于BNSTALG卵圆核的CRF神经元。重复束缚应激（RRS）后，动物表现出焦虑样行为的显著增加，这与BNSTALG中STEP mRNA和蛋白表达的下调以及III型推定CRF神经元中诱导的长时程增强（LTP）的选择性增强幅度相关。为了确定RRS后STEP表达的变化是否与突触强化的促进机制相关，我们研究了细胞内应用STEP对LTP诱导的影响。STEP完全阻断RRS诱导的BNSTALG神经元LTP易化。因此，STEP的作用是缓冲CRF神经元过度激活，而慢性应激后STEP的下调可能导致BNSTALG中CRF神经元的病理性激活，并导致长期的焦虑状态。因此，有针对性的STEP活动的操作可能是一种新的治疗策略，应激诱导的焦虑症。
STEP is a brain-specific protein tyrosine phosphatase that opposes the development of synaptic strengthening and the consolidation of fear memories. In contrast, stress facilitates fear memory formation, potentially by activating corticotrophin releasing factor (CRF) neurons in the anterolateral cell group of the bed nucleus of the stria terminalis (BNSTALG). Here, using dual-immunofluorescence, single-cell RT-PCR, quantitative RT-PCR, Western blot, and whole cell patch-clamp electrophysiology, we examined the expression and role of STEP in regulating synaptic plasticity in rat BNSTALG neurons, and its modulation by stress. STEP was selectively expressed in CRF neurons in the oval nucleus of the BNSTALG. Following repeated restraint stress (RRS), animals displayed a significant increase in anxiety-like behavior, which was associated with a down-regulation of STEP mRNA and protein expression in the BNSTALG as well as selectively enhanced magnitude of long-term potentiation (LTP) induced in Type III, putative CRF neurons. To determine if the changes in STEP expression following RRS were mechanistically related to the facilitation of synaptic strengthening, we examined the effects of intracellular application of STEP on the induction of LTP. STEP completely blocked the RRS-induced facilitation of LTP in BNSTALG neurons. Hence, STEP acts to buffer CRF neurons against excessive activation, while down-regulation of STEP after chronic stress may result in pathological activation of CRF neurons in the BNSTALG and contribute to prolonged states of anxiety. Thus, targeted manipulations of STEP activity might represent a novel treatment strategy for stress-induced anxiety disorders.
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影响因子：
3.4
作者：
Braithwaite, Steven P.;Adkisson, Michael;Nikolich, Karoly
通讯作者：
Nikolich, Karoly
影响因子：
--
作者：
MERCHENTHALER, I;VIGH, S;SCHALLY, AV
通讯作者：
SCHALLY, AV
DOI：
10.1073/pnas.0905568107
发表时间：
2010-02-02
影响因子：
11.1
作者：
McElligott, Zoe A.;Klug, Jason R.;Winder, Danny G.
通讯作者：
Winder, Danny G.
DOI：
10.1073/pnas.88.16.7242
发表时间：
1991-08-01
影响因子：
11.1
作者：
LOMBROSO, PJ;MURDOCH, G;LERNER, M
通讯作者：
LERNER, M
影响因子：
5.3
作者：
Choi, Dennis C.;Furay, Amy R.;Herman, James P.
通讯作者：
Herman, James P.