Blockade of TrkB receptors in the nucleus accumbens prior to heterotypic stress alters corticotropin-releasing hormone (CRH), vesicular glutamate transporter 2 (vGluT2) and glucocorticoid receptor (GR) within the mesolimbic pathway
Blockade of TrkB receptors in the nucleus accumbens prior to heterotypic stress alters corticotropin-releasing hormone (CRH), vesicular glutamate transporter 2 (vGluT2) and glucocorticoid receptor (GR) within the mesolimbic pathway
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DOI：
10.1016/j.yhbeh.2017.02.012
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发表时间：
2017-04-01
影响因子：
3.5
通讯作者：
Plamondon, Helene
中科院分区：
文献类型：
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作者：
Azogu, Idu;Plamondon, Helene
在奖赏通路中抑制应激诱导的脑源性神经营养因子（BDNF）或其主要受体酪氨酸相关激酶B（Trk B）的升高可以调节对焦虑和情绪障碍的易感性。目前的研究探讨了BDNF/TrkB信号传导在基础条件下和暴露于雄性大鼠10天异型应激范式后对生物化学和行为的作用。确定TrkB拮抗剂ANA-12（0.25 μ g/0.5 μ l/min）的脑内给药对焦虑的影响，以及Trk-B、促肾上腺皮质激素释放激素（CRH）、囊泡谷氨酸转运蛋白2（vGluT 2）和糖皮质激素受体（GR）在中脑边缘通路内的表达。值得注意的是，ANA-12减弱了应激大鼠的焦虑样行为，而增加了高架十字迷宫（ESTA）中非应激组的焦虑。在神经化学水平，ANA-12可阻断应激大鼠下丘脑室旁核和基底外侧杏仁核vGluT 2和CRH的表达，而增强非应激大鼠vGluT 2和CRH的表达。ANA-12在NAc核心也表现出状态依赖性作用，在非应激大鼠中减弱TrkB-ir，同时逆转应激大鼠中减少的表达。在扣带皮层，ANA-12使应激诱导的TrkB表达增加正常化。值得注意的是，ANA-12表现出区域特异性影响GR-IR在NAc的核心和外壳，增加GR-IR在非应激大鼠，虽然药物衰减应激诱导的GR-IR表达仅在核心部分的NAc，而没有影响扣带皮层。应激后升高的血CORT水平不受ANA-12治疗的影响。总之，这些研究结果表明，BDNF介导的TrkB激活在基础和应激条件下调节情绪反应时产生不同的影响。(C)2017爱思唯尔公司All rights reserved.
Inhibition of stress-induced elevations in brain-derived neurotrophic factor (BDNF) or its primary receptor tyrosine -related kinase B (TrkB) within the reward pathway may modulate vulnerability to anxiety and mood disorders. The current study examined the role of BDNF/TrkB signaling on biochemistry and behavior under basal conditions and following exposure to a 10-day heterotypic stress paradigm in male rats. Effects of intra-accumbal administration of TrkB antagonist ANA-12 (0.25 mu g/0.5 mu l/min) on anxiety, and expression of Trk-B, corticotropin-releasing hormone (CRH), vesicular glutamate transporter 2 (vGluT2) and glucocorticoid receptor (GR) within the mesolimbic pathway were determined. Notably, ANA-12 attenuated anxiety-like behavior in stress rats while increasing anxiety in the non-stress group in the elevated plus maze (EPM). At the neurochemical level, ANA-12 blocked the increased vGluT2 and CRH expressions in the hypothalamic PVN and basolateral amygdala in stress rats, while it enhanced vGluT2 and CRH expressions in non-stress rats. ANA-12 also showed state-dependent effects at the NAc core, attenuating TrkB-ir in non-stress rats while reversing reduced expression in stressed rats. At the cingulate cortex, ANA-12 normalized stress-induced increase in TrkB expression. Notably, ANA-12 showed region-specific effects on GR-ir at the NAc core and shell, with increased GR-ir in non-stress rats, although the drug attenuated stress-induced GR-ir expression only in the core portion of the NAc, while having no impact at the cingulate cortex. Elevated blood CORT levels post-stress was not influenced by ANA-12 treatment. Together, these findings suggest that BDNF-mediated TrkB activation exerts differential impact in regulating emotional response under basal and stress conditions. (C) 2017 Elsevier Inc. All rights reserved.