Differential roles of hippocampal glutamatergic receptors in neuropathic anxiety-like behavior after partial sciatic nerve ligation in rats.
Differential roles of hippocampal glutamatergic receptors in neuropathic anxiety-like behavior after partial sciatic nerve ligation in rats.
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DOI：
10.1186/s12868-015-0150-x
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发表时间：
2015-03-14
期刊：
影响因子：
2.4
通讯作者：
Bi FF
中科院分区：
文献类型：
--
作者：
Wang XQ;Zhong XL;Li ZB;Wang HT;Zhang J;Li F;Zhang JY;Dai RP;Xin-Fu Z;Li CQ;Li ZY;Bi FF
由神经损伤引起的神经病理性疼痛常常伴随着情绪行为的恶化，但其潜在的信号传导机制仍然不清楚。谷氨酸（Glu）是整个大脑兴奋性突触传递的主要介质，并且谷氨酸能系统的异常活动与疼痛的病理生理学和相关的情感共病有关。在这项研究中，我们使用了部分坐骨神经结扎（PSNL）模型的神经病理性疼痛大鼠的焦虑样行为的发展，海马神经元受体的表达，和细胞外信号调节激酶（ERK）的磷酸化，在海马区，编码与情绪相关的记忆。我们发现，机械退缩阈值显着降低，焦虑样行为增加，通过开放领域的测试和高架十字迷宫测试，在28天后受伤。蔗糖偏好实验和强迫游泳实验的蔗糖偏好率和不动时间差异不显著，可能与时间因素有关。损伤大鼠海马中N-甲基-D-天冬氨酸（NMDA）受体亚型NR 1和NR 2B的表达显著降低，而NR 2A、GluR 1和GluR 2（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸[AMPA]受体的主要亚型）的表达则没有显著降低。此外，PSNL导致海马ERK 1/2磷酸化水平降低。有趣的是，用D-丝氨酸（NMDA受体的共激动剂，1 g/kg腹腔注射）治疗减少了焦虑样行为，但没有减少PSNL诱导的机械超敏反应。PSNL可诱导大鼠出现焦虑样行为，但不诱导抑郁样行为，并在伤后28天下调海马NMDA受体，但不下调AMPA受体。
Neuropathic pain evoked by nerve injury is frequently accompanied by deterioration of emotional behaviors, but the underlying signaling mechanisms remain elusive. Glutamate (Glu) is the major mediator of excitatory synaptic transmission throughout the brain, and abnormal activity of the glutamatergic system has been implicated in the pathophysiology of pain and associated emotional comorbidities. In this study we used the partial sciatic nerve ligation (PSNL) model of neuropathic pain in rats to characterize the development of anxiety-like behavior, the expression of glutamatergic receptors, and the phosphorylation of extracellular signal-regulated kinase (ERK) in the hippocampus, the region that encodes memories related to emotions. We found that the mechanical withdrawal threshold was significantly reduced and an anxiety-like behavior was increased as determined via open field tests and elevated plus-maze tests at 28 days after injury. No significant differences were found in the ratio of sucrose preference and immobility time detected by sucrose preference tests and forced swimming tests respectively, possibly due to the timing factor. The expression of N-methyl-D-aspartate (NMDA) receptor subtypes NR1 and NR2B, but not NR2A, GluR1, or GluR2 (the main subtype of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] receptor) in the hippocampus of injured rats was significantly reduced. Moreover, PSNL resulted in decreased phosphorylation of ERK1/2 in the hippocampus. Intriguingly, treatment with D-serine (a co-agonist of NMDA receptor, 1 g/kg intraperitoneally) reduced the anxiety-like behavior but not the mechanical hypersensitivity induced by PSNL. PSNL can induce significant anxiety-like but not depression-like behavior, and trigger down-regulation of NMDA but not AMPA receptors in the hippocampus at 28 days after injury.
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