β-Adrenergic Receptor Antagonism Prevents Anxiety-like Behavior and Microglial Reactivity Induced by Repeated Social Defeat

By E. Wohleb, Mark L. Hanke, Angela W. Corona, N. Powell, La’Tonia M. Stiner, M. Bailey, R. Nelson, Jonathan P. Godbout, J. Sheridan. Journal of Neuroscience, 2011

621 citations recorded by the source corpus.

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+/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) 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.

Subfields: Behavioral Neuroscience, Biological Psychiatry, Neurology

View Paper: https://www.semanticscholar.org/paper/c0e2205a1c67b7384dc7b21d25d8a96845ee7432

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In Behavioral Neuroscience

1. Gregory E. Miller
2. Robin Nusslock
3. Oliver D. Howes

In Biological Psychiatry

1. Gregory E. Miller
2. Robin Nusslock
3. Oliver D. Howes

In Neurology

1. Gregory E. Miller
2. Robin Nusslock
3. Oliver D. Howes

Citations in the corpus

• Early-Life Adversity and Physical and Emotional Health across the Lifespan: A Neuro-Immune Network Hypothesis (2015, background): “Notably, mice lacking a functional receptor for interleukin-1β, a key inflammatory mediator, do not exhibit defeat-evoked microglial activation or anxiety behaviors (68).”
• Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness (2016, methodology): “…varying unpredictable stress → Rat Tynan et al. (2010) and Kopp et al. (2013) Prefrontal cortex Repeated social defeat, varying unpredictable stress ↑↑↑ Mouse Bian et al. (2012), Wohleb et al. (2011, 2012) Prenatal stress ↑↑ Rat Ślusarczyk et al. (2015) Social isolation, chronic restraint,…”