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Updated: Aug 15, 2025
A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
IGF2 inhibits hippocampal over-activated microglia and alleviates depression-like behavior in LPS- treated male mice
Dongming Guo1, Yang Xu2, Zhenghai Liu3
1Institute of Translational Medicine, Medical, Yangzhou University, 225009 Yangzhou, Jiangsu, China; Department of Human Anatomy, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China.
Abstract:
Over-activated microglia and inflammatory mediators are found in patients with depression, while manipulation of the microglia function might represent a potential therapeutic strategy. Insulin-like growth factor 2 (IGF2) has been implicated in bacterial infections and autoimmune disorders, but the role of IGF2 on the active phenotype of microglia and neuroinflammation has not been well established. IGF2 influences in modulating microglia responding to neuroinflammation induced by lipopolysaccharide（LPS）challenge will be carefully examined. In the current study, we verified that systemic IGF2 treatment could produce an anti-depression effect in LPS-treated mice. Particularly, we found that systemic IGF2 treatment inhibited microglia over-activation and prevented its transformation to a pro-inflammatory phenotype, thereby protecting hippocampal neurogenesis. Since microglia reactive to neuroinflammation is a common feature of neuropsychiatric disorders, the discoveries from the present study may provide therapeutic innovation for these diseases.
Insights
Insulin-like growth factor 2 (IGF2) shows antidepressant effects by reducing microglia over-activation and neuroinflammation. This finding offers potential therapeutic strategies for depression and other neuropsychiatric disorders.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Over-activated microglia and inflammatory mediators are linked to depression.
- The role of Insulin-like Growth Factor 2 (IGF2) in microglia activation and neuroinflammation is not well understood.
Purpose of the Study:
- To investigate the effect of IGF2 on microglia phenotype during lipopolysaccharide (LPS)-induced neuroinflammation.
- To determine if IGF2 administration has an anti-depression effect in a mouse model.
Main Methods:
- Systemic administration of IGF2 in lipopolysaccharide (LPS)-treated mice.
- Assessment of microglia activation state and pro-inflammatory markers.
- Evaluation of hippocampal neurogenesis.
Main Results:
- Systemic IGF2 treatment demonstrated an anti-depression effect in LPS-treated mice.
- IGF2 inhibited microglia over-activation and prevented their shift to a pro-inflammatory phenotype.
- IGF2 treatment protected hippocampal neurogenesis.
Conclusions:
- IGF2 modulates microglia response to neuroinflammation, suggesting a therapeutic potential.
- IGF2 may offer a novel therapeutic strategy for depression and other neuropsychiatric disorders characterized by neuroinflammation.
