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Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C)
Published on: March 25, 2016
Microglial IL-27 modulates depression-like behaviors induced by postnatal immune activation
Xinghui Qiao1, Naigang Li1, Yuan Yao1
1Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Mental Disorders and Intelligent Control, School of Basic Medical Sciences, Shandong University Affiliated Children's Hospital, Shandong University, Jinan, Shandong 250012, China.
Interleukin-27 (IL-27) signaling in microglia mitigates depression-like behaviors caused by early-life inflammation. This neuroimmune interaction preserves synaptic density, offering therapeutic potential for mood disorders.
Area of Science:
- Neuroimmunology
- Neurodevelopmental Disorders
- Psychiatry
Background:
- Early-life inflammation is linked to increased risk of mental disorders.
- Neuroinflammation impacts microglial function and synaptic integrity.
- Mechanisms of local immune signal modulation of microglia remain unclear.
Purpose of the Study:
- To investigate the role of microglia-associated IL-27-IL-27Rα signaling in mitigating depression-like behaviors.
- To elucidate the cellular and molecular mechanisms underlying IL-27's protective effects.
- To evaluate the therapeutic potential of IL-27 for mood disorders.
Main Methods:
- Postnatal immune activation (PIA) model in mice.
- IL-27 administration and assessment of behavioral deficits.
- Analysis of microglial phagocytic activity and synaptic density.
- Investigation of STAT1-Trem2 signaling pathway.
Main Results:
- IL-27 treatment alleviated depression-like behaviors in PIA mice.
- IL-27 suppressed excessive microglial phagocytosis, preserving synaptic density.
- Beneficial effects were observed in prenatal stress models.
- IL-27 administration was well-tolerated in animal safety evaluations.
- STAT1-Trem2 pathway partially mediated the effects.
Conclusions:
- Microglia-associated IL-27-IL-27Rα signaling is a protective mechanism against early-life inflammation-induced depression.
- IL-27 preserves synaptic integrity by modulating microglial phagocytosis.
- IL-27 demonstrates therapeutic potential for mood disorders linked to neurodevelopmental immune dysregulation.
