Injection of Anti-proBDNF Attenuates Hippocampal-Dependent Learning and Memory Dysfunction in Mice With Sepsis-Associated Encephalopathy.
Injection of Anti-proBDNF Attenuates Hippocampal-Dependent Learning and Memory Dysfunction in Mice With Sepsis-Associated Encephalopathy.
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注射抗-proBDNF 可减轻脓毒症相关脑病小鼠海马依赖性学习和记忆功能障碍
DOI：
10.3389/fnins.2021.665757
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发表时间：
2021
影响因子：
4.3
通讯作者：
Li CQ
中科院分区：
文献类型：
--
作者：
Cui YH;Zhou SF;Liu Y;Wang S;Li F;Dai RP;Hu ZL;Li CQ
脓毒症相关脑病（SAE）是认知和记忆功能障碍的风险因素;然而，其机制仍不清楚。脑源性神经营养因子（Brain-derived neurotrophic factor，BDNF）在认知和情绪调节中具有积极作用，但其前体proBDNF的研究还很有限。本研究旨在阐明海马BDNF原在脂多糖（LPS）诱导的SAE小鼠模型中的作用及其相关机制。在这项研究中，我们发现小鼠在LPS注射后第7天表现出认知功能障碍。海马中proBDNF及其受体p75 NTR的表达也增加，而BDNF及其受体TrkB的水平降低。共定位研究显示proBDNF和p75 NTR主要与神经元共定位。此外，LPS处理降低SAE小鼠海马中NeuN、尼氏体、GluR 4、NR 1、NR 2A和NR 2B的表达。此外，海马内或腹腔内注射抗proBNP抗体能够改善LPS诱导的认知功能障碍并恢复NeuN、尼氏体、GluR 4、NR 1、NR 2A、NR 2B和PSD 95的表达。这些结果表明，通过海马内和全身注射mAb-proBDNF进行脑递送的治疗可能代表治疗SAE患者的潜在治疗策略。
Sepsis-associated encephalopathy (SAE) is a risk factor for cognitive and memory dysfunction; however, the mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) was reported to have a positive effect on cognition and emotion regulation, but the study of its precursor, proBDNF, has been limited. This study aimed to elucidate the effects and associated mechanisms of hippocampal proBDNF in a lipopolysaccharide (LPS)-induced SAE mouse model. In this study, we found that the mice exhibited cognitive dysfunction on day 7 after LPS injection. The expression of proBDNF and its receptor, p75NTR, was also increased in the hippocampus, while the levels of BDNF and its receptor, TrkB, were decreased. A co-localization study showed that proBDNF and p75NTR were mainly co-localized with neurons. Furthermore, LPS treatment reduced the expression of NeuN, Nissl bodies, GluR4, NR1, NR2A, and NR2B in the hippocampus of SAE mice. Furthermore, an intrahippocampal or intraperitoneal injection of anti-proBDNF antibody was able to ameliorate LPS-induced cognitive dysfunction and restore the expression of NeuN, Nissl bodies, GluR4, NR1, NR2A, NR2B, and PSD95. These results indicated that treatment with brain delivery by an intrahippocampal and systemic injection of mAb-proBDNF may represent a potential therapeutic strategy for treating patients with SAE.
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影响因子：
3
作者：
Kadar, Andrea;Wittmann, Gabor;Liposits, Zsolt;Fekete, Csaba
通讯作者：
Fekete, Csaba
p75 神经营养素受体可能介导脓毒症引起的突触和认知障碍
影响因子：
2.7
作者：
Ji, Muhuo;Yuan, Hongmei;Yang, Jianjun
通讯作者：
Yang, Jianjun
影响因子：
7.6
作者：
Bai, Yin-Yin;Ruan, Chun-Sheng;Zhou, Xin-Fu
通讯作者：
Zhou, Xin-Fu
影响因子：
5.2
作者：
Fink MP
通讯作者：
Fink MP
影响因子：
56.3
作者：
Cohen, Jonathan;Vincent, Jean-Louis;Pelfrene, Eric
通讯作者：
Pelfrene, Eric