Repeated norepinephrine receptor stimulation in the BNST induces sensorimotor gating deficits via corticotropin releasing factor.
Repeated norepinephrine receptor stimulation in the BNST induces sensorimotor gating deficits via corticotropin releasing factor.
复制标题
BNST 中去甲肾上腺素受体的重复刺激可通过促肾上腺皮质激素释放因子诱导感觉运动门控缺陷。
DOI：
10.1016/j.neuropharm.2020.108090
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发表时间：
2020
影响因子：
4.7
通讯作者：
Bakshi,VaishaliP
中科院分区：
文献类型：
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作者：
Rajbhandari,AbhaKarki;Bakshi,VaishaliP
强烈的压力会引发创伤后应激障碍（PTSD）和精神分裂症等疾病的症状。这些疾病的患者有感觉运动门控功能失调，表现为惊吓反应（PPI）的脉冲前抑制中断，这是指当一个弱的预刺激先于一个惊吓刺激时，惊吓反应下降。压力促进大脑内去甲肾上腺素（NE）和促肾上腺皮质激素释放因子（CRF）的释放，这些神经递质也能调节PPI。我们已经证明，反复的应激会通过CRF受体导致基底外侧杏仁核（BLA）内的NE受体致敏，并促进持久的PPI中断和惊吓异常。终纹床核（BNST）是另一个重要的大脑区域，它可能参与应力诱导的NE和CRF功能改变，从而促进PPI的变化，因为该解剖结构富含CRF和NE受体，这两种受体已被证明是相互调节的。我们假设反复向BNST注入NE会使CRF受体交叉敏感，反之亦然，从而改变PPI。各组雄性sd大鼠分别注射CRF （200ng/0.5 μl）、NE （20μg/0.5 μl）或载药，每天1次，连续3 d，每次注射后检测PPI。然后用亚阈剂量的NE （0.3μg/0.5 μl）刺激重复剂量的CRF （200ng/0.5 μl）刺激重复剂量的CRF或载药处理大鼠，测定PPI。令人惊讶的是，BNST中初始/重复的CRF或车辆对PPI没有影响。相反，初始和重复的NE破坏了PPI。先前接受重复CRF的大鼠的亚阈值NE刺激对PPI没有影响。然而，有趣的是，在先前多次接受NE输注的大鼠中，bnst内的CRF攻击剂量显著破坏了PPI。综上所述，这些结果表明，反复应激诱导的NE释放可以改变BNST中CRF受体的活性，从而调节感觉运动门控（通过PPI测量）。
Intense stress precipitates symptoms in disorders such as post-traumatic stress (PTSD) and schizophrenia. Patients with these disorders have dysfunctional sensorimotor gating as indexed by disrupted prepulse inhibition of the startle response (PPI), which refers to decreased startle response when a weak pre-stimulus precedes a startling stimulus. Stress promotes release of norepinephrine (NE) and corticotrophin releasing factor (CRF) within the brain, neurotransmitters that also modulate PPI. We have shown that repeated stress causes sensitization of NE receptors within the basolateral amygdala (BLA) via CRF receptors and promotes long-lasting PPI disruptions and startle abnormalities. The bed nucleus of the stria terminalis (BNST) is another crucial brain region that could be involved in stress-induced alterations in NE and CRF functions to promote PPI changes as this anatomical structure is enriched in CRF and NE receptors that have been shown to regulate each other. We hypothesized that repeated infusions of NE into the BNST would cross-sensitize CRF receptors or vice versa to alter PPI. Separate groups of male Sprague Dawley rats received, CRF (200ng/0.5 μl), NE (20μg/0.5 μl), or vehicle into the BNST, once/day for 3 days and PPI was tested after each infusion. Repeated CRF-or vehicle-treated rats were then challenged with a subthreshold dose of NE (0.3μg/0.5 μl) while repeated NE-treated rats were challenged with CRF (200ng/0.5 μl), and PPI was measured. Surprisingly, initial/repeated CRF or vehicle in the BNST had no effects on PPI. In contrast, initial and repeated NE disrupted PPI. Sub-threshold NE challenge in rats that previously received repeated CRF had no effect on PPI. Interestingly though, intra-BNST challenge dose of CRF significantly disrupted PPI in rats that previously had received repeated NE infusions. Taken together, these results indicate that repeated stress-induced NE release could alter the activity of CRF receptors in the BNST to modulate sensorimotor gating as measured through PPI.