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Stress-Induced Neuronal Colony Stimulating Factor 1 Provokes Microglia-Mediated Neuronal Remodeling and

Eric S Wohleb1, Rosemarie Terwilliger2, Catharine H Duman2

  • 1Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Biological Psychiatry
|July 13, 2017
PubMed
Summary

Chronic stress increases neuronal colony stimulating factor 1 (CSF1) in the medial prefrontal cortex, activating microglia. This leads to synaptic deficits and anxiety-like behaviors, highlighting a key mechanism in stress-related disorders.

Keywords:
Colony stimulating factor 1DepressionMicrogliaNeuroimmunePrefrontal cortexStress

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Area of Science:

  • Neuroscience
  • Neuroimmunology
  • Behavioral Neuroscience

Background:

  • Chronic stress induces neuronal atrophy and synaptic deficits in the medial prefrontal cortex (PFC), contributing to anxiety and depression.
  • Microglia in the PFC exhibit altered morphology and function post-stress, suggesting their role in stress-induced synaptic deficits.

Purpose of the Study:

  • To investigate the role of neuron-microglia interactions in the medial PFC during the development of anxiety- and depressive-like behaviors following chronic unpredictable stress (CUS).
  • To examine the impact of neuronal colony stimulating factor 1 (CSF1) on microglia function and associated behavioral outcomes after CUS.

Main Methods:

  • Exposure of male and female mice to CUS.
  • Utilized Thy1-GFP-M mice to assess microglia-mediated neuronal remodeling and dendritic spine density in the medial PFC.
  • Employed viral-mediated knockdown of neuronal CSF1 to modulate microglia function and behavioral responses.

Main Results:

  • CUS induced anxiety- and depressive-like behaviors, correlating with increased CSF1 mRNA in the PFC, also observed in human depression cases.
  • Microglia from stressed mice showed elevated CSF1 receptor expression and increased neuronal phagocytosis, more pronounced in males.
  • Reduced dendritic spine density was observed in medial PFC layer 1 pyramidal neurons, and CSF1 knockdown attenuated these changes and prevented behavioral deficits.

Conclusions:

  • Stress-induced elevations in neuronal CSF1 trigger microglia-mediated neuronal remodeling in the medial PFC.
  • This process contributes to synaptic deficits and the manifestation of anxiety- and depressive-like behaviors.