Source Paper
β-Adrenergic Receptor Antagonism Prevents Anxiety-Like Behavior and Microglial Reactivity Induced by Repeated Social Defeat
Eric S. Wohleb, et al.
Source Paper
Eric S. Wohleb, et al.
Journal of Neuroscience • 2011
Psychosocial stress is associated with altered immune function and development of psychological disorders including anxiety and depression. Here we show that repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner. Repeated social defeat also significantly increased the number of CD11b + /CD45 high /Ly6C high macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat. Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus. Moreover, mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]. The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist. Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide compared with microglia from control mice. Last, repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1. These findings indicate that repeated social defeat-induced anxiety-like behavior and enhanced reactivity of microglia was dependent on activation of β-adrenergic and IL-1 receptors.
Objective: To determine if repeated social defeat induces anxiety-like behavior and microglial reactivity through β-adrenergic receptor signaling and IL-1 receptor activation
This is a Repeated Social Defeat protocol using mouse as the model organism. The procedure involves 9 procedural steps, 1 equipment items, 2 materials. Extracted from a 2011 paper published in Journal of Neuroscience.
Model and subjects
mouse • Not explicitly stated in provided text • Not explicitly stated in provided text • Not explicitly stated in provided text • Not explicitly stated in provided text • Not explicitly stated in provided text
Study window
Estimated timing pending
Core workflow
Repeated Social Defeat Exposure • Behavioral Testing for Anxiety • Brain Tissue Collection and c-Fos Staining
Primary readouts
Key equipment and reagents
Verified items
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Mice were exposed to repeated social defeat stress paradigm to induce anxiety-like behavior and immune alterations
Note: This is a psychosocial stress paradigm where mice experience repeated social defeat
“Repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior”
Anxiety-like behavior was assessed following repeated social defeat exposure
Note: β-adrenergic receptor-dependent anxiety-like behavior was measured
“Repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner”
Brain tissue was collected and analyzed for c-Fos staining in regions associated with fear and threat appraisal
Note: c-Fos staining was increased in brain regions associated with fear and threat appraisal
“Repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal”
Analysis of CD11b+/CD45high/Ly6Chigh macrophages that trafficked to the brain and inflammatory markers on microglia and macrophages
Note: Markers analyzed included CD14, CD86, and TLR4 on microglia and macrophages
“Repeated social defeat also significantly increased the number of CD11b+/CD45high/Ly6Chigh macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86)”
Assessment of microglial morphology in medial amygdala, prefrontal cortex, and hippocampus to identify deramified microglia
Note: Deramified microglia presence was increased in these brain regions
“Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus”
mRNA analysis of microglia to measure interleukin (IL)-1β and glucocorticoid responsive genes (GILZ and FKBP51)
Note: Repeated social defeat increased IL-1β levels and reduced GILZ and FKBP51 levels
“mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]”
Administration of propranolol (β-adrenergic receptor antagonist) to prevent stress-dependent changes in microglia and macrophages
Note: Propranolol prevented the stress-dependent changes in microglia and macrophages
“The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist”
Microglia were isolated from socially defeated and control mice, cultured ex vivo, and stimulated with lipopolysaccharide
Note: Microglia from defeated mice produced higher levels of IL-6, TNF-α, and MCP-1
“Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide”
Repeated social defeat was tested in IL-1 receptor type-1-deficient mice to assess IL-1 receptor dependence
Note: Social defeat increased c-Fos activation but did not promote anxiety-like behavior or microglia activation in IL-1R1-deficient mice
“Repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1”
This section explains what the experiment is doing, which readouts matter, what the data artifacts usually look like, and how the analysis should flow from raw capture to reported result.
To determine if repeated social defeat induces anxiety-like behavior and microglial reactivity through β-adrenergic receptor signaling and IL-1 receptor activation
Objective
To determine if repeated social defeat induces anxiety-like behavior and microglial reactivity through β-adrenergic receptor signaling and IL-1 receptor activation
Subjects
From papermouse • Not explicitly stated in provided text • Not explicitly stated in provided text • Not explicitly stated in provided text • Not explicitly stated in provided text
Sample count
From paperNot explicitly stated in provided text
Cohort notes
From paperIL-1 receptor type-1-deficient mice were used in some experiments
Repeated Social Defeat Exposure (Not explicitly specified in provided text)
Behavioral Testing for Anxiety (Not specified)
Brain Tissue Collection and c-Fos Staining (Not specified)
Flow Cytometry Analysis of Immune Cells (Not specified)
C-Fos staining in brain regions associated with fear and threat appraisal
From paperNot explicitly detailed in provided text
Artifact type
Representative image panels with region or marker comparisons
Comparison focus
Compare staining intensity, structure, or cell counts across matched conditions
Anxiety-like behavior
From paperNot explicitly detailed in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
CD11b+/CD45high/Ly6Chigh macrophage trafficking to brain
From paperNot explicitly detailed in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Inflammatory markers on microglia surface (CD14, CD86, TLR4)
From paperNot explicitly detailed in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
C-Fos staining in brain regions associated with fear and threat appraisal
From paperRaw artifact
Field or section images captured from matched samples
Processed artifact
Selected representative panels with quantified intensity, counts, or area measurements
Final reported form
Per-group imaging summaries with representative figures and quantified endpoints
Anxiety-like behavior
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
CD11b+/CD45high/Ly6Chigh macrophage trafficking to brain
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Inflammatory markers on microglia surface (CD14, CD86, TLR4)
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
Preprocessing / cleaning
Not explicitly detailed in provided text
Scoring or quantification
Quantify the primary readouts for this experiment: C-Fos staining in brain regions associated with fear and threat appraisal; Anxiety-like behavior; CD11b+/CD45high/Ly6Chigh macrophage trafficking to brain; Inflammatory markers on microglia surface (CD14, CD86, TLR4).
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for C-Fos staining in brain regions associated with fear and threat appraisal, Anxiety-like behavior, CD11b+/CD45high/Ly6Chigh macrophage trafficking to brain, Inflammatory markers on microglia surface (CD14, CD86, TLR4).
Source links and direct wording from the methods section for validation and deeper review.
Citation
Eric S. Wohleb et al. (2011). β-Adrenergic Receptor Antagonism Prevents Anxiety-Like Behavior and Microglial Reactivity Induced by Repeated Social Defeat. Journal of Neuroscience
Repeated Social Defeat Exposure • Protocol step
“Repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior”
Behavioral Testing for Anxiety • Protocol step
“Repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner”
Brain Tissue Collection and c-Fos Staining • Protocol step
“Repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal”
Flow Cytometry Analysis of Immune Cells • Protocol step
“Repeated social defeat also significantly increased the number of CD11b+/CD45high/Ly6Chigh macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86)”
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