Neuropeptide VGF C-Terminal Peptide TLQP-62 Alleviates Lipopolysaccharide-lnduced Memory Deficits and Anxiety-like and Depression-like Behaviors in Mice: The Role of BDNF/TrkB Signaling
Neuropeptide VGF C-Terminal Peptide TLQP-62 Alleviates Lipopolysaccharide-lnduced Memory Deficits and Anxiety-like and Depression-like Behaviors in Mice: The Role of BDNF/TrkB Signaling
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神经肽 VGF C 端肽 TLQP-62 减轻脂多糖诱导的小鼠记忆缺陷以及焦虑样和抑郁样行为：BDNF/TrkB 信号传导的作用
DOI：
10.1021/acschemneuro.7b00154
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发表时间：
2017-09-01
影响因子：
5
通讯作者：
Wang, Chuang
中科院分区：
文献类型：
--
作者：
Li, Chenli;Li, Mengmeng;Wang, Chuang
周围炎症反应影响中枢神经系统 (CNS) 功能，表现为记忆缺陷、抑郁和焦虑症状。先前的研究表明，神经肽 VGF（非缩写）C 末端肽 TLQP-62 可以快速增强脑源性神经营养因子 (BDNF)/原肌球蛋白受体激酶 B (TrkB) 信号传导，调节记忆巩固和抗抑郁样作用。然而，它是否对脂多糖（LPS）诱导的小鼠神经精神功能障碍有益尚不清楚。在此，我们探讨了 BDNF/TrkB 信号传导和炎症或氧化应激标志物的生化改变在 TLQP-62 对 LPS 诱导的神经精神功能障碍的缓解作用中的作用。在LPS（0.5 mg/kg，腹腔注射）给药前1小时，通过脑室内（i.c.v.）注射TLQP-62（2 g/侧）治疗小鼠。我们的结果表明，单次 LPS（0.5 mg/kg，腹腔注射）治疗足以产生识别记忆缺陷（在新物体识别测试中）、抑郁样行为（在强迫游泳测试和蔗糖偏好测试中）和焦虑样行为（在高架零迷宫中）。然而，TLQP-62 预处理可防止 LPS 诱导的行为功能障碍、神经炎症和氧化反应。此外，我们的结果进一步证明，BDNF-shRNA慢病毒介导的BDNF表达减少显着阻断了TLQP-62的作用，表明BDNF/TrkB信号在TLQP-62对小鼠的神经保护作用中发挥着关键作用。总之，TLQP-62可能是神经精神疾病的一种治疗方法，神经精神疾病与神经炎症和氧化应激密切相关。
Peripheral inflammatory responses affect central nervous system (CNS) function, manifesting in symptoms of memory deficits, depression, and anxiety. Previous studies have revealed that neuropeptide VGF (nonacronymic) C terminal peptide TLQP-62 rapidly reinforces brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling, regulating memory consolidation and antidepressant-like action. However, whether it is beneficial for lipopolysaccharide (LPS)-induced neuropsychiatric dysfunction in mice is unknown Herein, we explored the involvement of BDNF/TrkB signaling and biochemical alterations in inflammatory or oxidative stress markers in the alleviating effects of TLQP-62 on LPS-induced neuropsychiatric dysfunction. The mice were treated with TLQP-62 (2 g/side) via intracerebroventricular (i.c.v.) injection 1 h before LPS (0.5 mg/kg, i.p.) administration. Our results showed that a single treatment with LPS (0.5 mg/kg, i.p) is sufficient to produce recognition memory deficits (in the novel object recognition test), depression-like behavior (in the forced swim test and sucrose preference test), and anxiety-like behavior (in the elevated zero maze). However, pretreatment with TLQP-62 prevented LPS-induced behavioral dysfunction, neuroinflammatory, and oxidative responses. In addition, our results further demonstrated that a reduction in BDNF expression mediated by BDNF-shRNA lentivirus significantly blocked the effects of TLQP-62, suggesting the critical role of BDNF/TrkB signaling in the neuroprotective effects of TLQP-62 in the mice. In conclusion, TLQP-62 could be a therapeutic approach for neuropsychiatric disorders, which are closely associated with neuroinflammation and oxidative stress.