Injection of Anti-proBDNF Attenuates Hippocampal-Dependent Learning and Memory Dysfunction in Mice With Sepsis-Associated Encephalopathy
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...
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doaj-f7014262cc7647d5a05a279d173373d42021-07-20T09:13:46ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-07-011510.3389/fnins.2021.665757665757Injection of Anti-proBDNF Attenuates Hippocampal-Dependent Learning and Memory Dysfunction in Mice With Sepsis-Associated EncephalopathyYan-Hui Cui0Yan-Hui Cui1Shi-Fen Zhou2Yu Liu3Yu Liu4Shuang Wang5Fang Li6Ru-Ping Dai7Zhao-Lan Hu8Chang-Qi Li9Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, ChinaDepartment of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, ChinaDepartment of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, ChinaDepartment of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Medical Research Center and Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, ChinaDepartment of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, ChinaSepsis-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.https://www.frontiersin.org/articles/10.3389/fnins.2021.665757/fullsepsis associated encephalopathyproBDNFp75NTRhippocampuscognition and memory dysfunction |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yan-Hui Cui Yan-Hui Cui Shi-Fen Zhou Yu Liu Yu Liu Shuang Wang Fang Li Ru-Ping Dai Zhao-Lan Hu Chang-Qi Li |
spellingShingle |
Yan-Hui Cui Yan-Hui Cui Shi-Fen Zhou Yu Liu Yu Liu Shuang Wang Fang Li Ru-Ping Dai Zhao-Lan Hu Chang-Qi Li Injection of Anti-proBDNF Attenuates Hippocampal-Dependent Learning and Memory Dysfunction in Mice With Sepsis-Associated Encephalopathy Frontiers in Neuroscience sepsis associated encephalopathy proBDNF p75NTR hippocampus cognition and memory dysfunction |
author_facet |
Yan-Hui Cui Yan-Hui Cui Shi-Fen Zhou Yu Liu Yu Liu Shuang Wang Fang Li Ru-Ping Dai Zhao-Lan Hu Chang-Qi Li |
author_sort |
Yan-Hui Cui |
title |
Injection of Anti-proBDNF Attenuates Hippocampal-Dependent Learning and Memory Dysfunction in Mice With Sepsis-Associated Encephalopathy |
title_short |
Injection of Anti-proBDNF Attenuates Hippocampal-Dependent Learning and Memory Dysfunction in Mice With Sepsis-Associated Encephalopathy |
title_full |
Injection of Anti-proBDNF Attenuates Hippocampal-Dependent Learning and Memory Dysfunction in Mice With Sepsis-Associated Encephalopathy |
title_fullStr |
Injection of Anti-proBDNF Attenuates Hippocampal-Dependent Learning and Memory Dysfunction in Mice With Sepsis-Associated Encephalopathy |
title_full_unstemmed |
Injection of Anti-proBDNF Attenuates Hippocampal-Dependent Learning and Memory Dysfunction in Mice With Sepsis-Associated Encephalopathy |
title_sort |
injection of anti-probdnf attenuates hippocampal-dependent learning and memory dysfunction in mice with sepsis-associated encephalopathy |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2021-07-01 |
description |
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. |
topic |
sepsis associated encephalopathy proBDNF p75NTR hippocampus cognition and memory dysfunction |
url |
https://www.frontiersin.org/articles/10.3389/fnins.2021.665757/full |
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