Dynamic Microglial Activation is Associated with LPS-induced Depressive-like Behavior in Mice: An [18F] DPA-714 PET Imaging Study

Authors

  • Tian Qiu Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. https://orcid.org/0000-0003-4104-7238
  • Jiamei Guo Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • Lixia Wang Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • Lei Shi Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • Ming Ai Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • Zhu Xia Department of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • Zhiping Peng Department of Radiological Medicine, College of Basic Medicine, Chongqing Medical University, Chongqing, China.
  • Li Kuang Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

DOI:

https://doi.org/10.17305/bjbms.2021.6825

Keywords:

depression, microglia, [18F] DPA-714, lipopolysaccharide, positron emission tomography

Abstract

Major depressive disorder (MDD) is a highly pervasive, severe psychological condition for which the precise underlying pathophysiology is incompletely understood, although microglial activation is known to play a role in this context. In this study we analyzed the association between neuroinflammation and depressive-like behaviors in a lipopolysaccharide (LPS)-induced mouse model system using 10-12-week-old male C57BL/6 mice. Microglial activation and associated neuroinflammatory activity were monitored via positron emission tomography (PET) imaging. Animals were assessed at three time points, including 24 h prior to LPS injection, 24 h post-LPS injection, and 72 h post-LPS injection. Analyses of microglial activation and hippocampal neuroinflammation were conducted through [18]F DPA-714 PET imaging and immunohistochemical staining for ionized calcium-binding adapter molecule 1 (Iba-1) and translocator protein (TSPO). Moreover, NOD-like receptor protein 3 (NLRP3) inflammasome activity and interleukin-1β (IL-1β) levels were assessed at 24 h post-LPS injection. We found that LPS treatment was associated with a marked increase in depressive-like behavior at 24 h post-injection time point, and that it was less pronounced at the 72 h post-injection time point. These changes coincided with enhanced [18F] DPA-714 PET uptake in the whole brain, hippocampus, cortex and amygdala together with increased hippocampal microglial activation as evidenced by immunofluorescent staining. By 72 h post-injection, however, these PET and immunofluorescence phenotypes had returned to baseline levels. Furthermore, increased NLRP3 inflammasome activation and IL-1β expression were evident at 24 h post-LPS injection. These data demonstrate that dynamic microglial activation is associated with LPS-induced depressive-like behaviors and hippocampal neuroinflammation in a mouse model system.

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Dynamic Microglial Activation is Associated with LPS-induced Depressive-like Behavior in Mice: An [18F] DPA-714 PET Imaging Study

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Published

2022-01-30

How to Cite

1.
Qiu T, Guo J, Wang L, Shi L, Ai M, Xia Z, Peng Z, Kuang L. Dynamic Microglial Activation is Associated with LPS-induced Depressive-like Behavior in Mice: An [18F] DPA-714 PET Imaging Study. Bosn J of Basic Med Sci [Internet]. 2022Jan.30 [cited 2022May24];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/6825

Issue

Section

New and Emerging Methods