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Author Spotlight: Induced Microglia-Like Cell Technology to Shed Light on the Role of Microglial Dysfunction in Neuropsychiatric Disorders
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Author Spotlight: Induced Microglia-Like Cell Technology to Shed Light on the Role of Microglial Dysfunction in Neuropsychiatric Disorders

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Replenished microglia partially rescue schizophrenia-related stress response

Ling Yan1, Fang-Ling Xuan1, Song Chen2

  • 1Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu, Tartu, Estonia.

Frontiers in Cellular Neuroscience
|September 29, 2023
PubMed
Abstract

Insights

Microglial replenishment shows promise for treating schizophrenia by improving stress-induced behavioral deficits and brain changes. This therapy may help restore brain homeostasis in psychiatric disorders.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Immunology

Background:

  • Microglia are crucial for brain and behavioral stability.
  • Microglial replenishment has shown benefits in neurological diseases.
  • Its efficacy in psychiatric disorders like schizophrenia, particularly stress-related forms, remains unclear.

Purpose of the Study:

  • To investigate the therapeutic potential of microglial replenishment in stress-associated schizophrenia.
  • To understand the mechanisms underlying microglial replenishment in the context of chronic stress.

Main Methods:

  • Utilized a CSF1R-mediated pharmacological approach for microglial replenishment in mice under chronic unpredictable stress (CUS).
  • Examined a cohort of first-episode schizophrenia (FES) patients and healthy controls (HCs), assessing perceived stress scores (PSS) and hippocampal fimbria size.
  • Analyzed differentially expressed genes (DEGs) in the prefrontal cortex and blood, and microglial morphology.

Main Results:

  • Microglial replenishment (repMg) mitigated CUS-induced learned hopelessness and social withdrawal in mice, but not anxiety.
  • CUS and repMg altered gene expression in the prefrontal cortex related to nervous system development and axonal guidance.
  • CUS induced microglial hyper-ramification and increased engulfment of synaptic components, which were reversed by repMg.
  • FES patients exhibited smaller hippocampal fimbria, negatively correlated with PSS.
  • Blood DEGs involved in immune system development were associated with PSS and fimbria size in FES patients.

Conclusions:

  • Microglial replenishment may offer a potential therapeutic strategy for psychiatric disorders like schizophrenia.
  • The findings suggest a role for microglial function and immune system pathways in the pathophysiology of stress-related schizophrenia.
Keywords:
chronic unpredictable stresshippocampusmicroglial replenishmentprefrontal cortexschizophreniasynaptic pruning

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