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A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
Published on: January 27, 2019
Morin exerts protective effects on encephalopathy and sepsis-associated cognitive functions in a murine sepsis model
Xi-E Xu1, Meng-Zhu Li2, En-Sheng Yao3
1Trauma Center/Department of Emergency and Trauma Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Sepsis-associated encephalopathy (SAE) often leads to cognitive impairments in the rest life of septic survivors. The potential pathological changes of SAE are complicated and have not been fully understood. Morin, a flavone compound exhibiting neuroprotective activity and anti-inflammation effect, was employed to treat with CLP-induced septic mice in our study. The data from a novel object recognition test and tail suspension test indicated that morin treatment reversed cognitive dysfunction and relieved depressive-like behaviors in septic mice. Morin down-regulated the expressions of IL-6, MCP-1, TNF-α and IL-10 in serum and diminished microglia activation in septic mice. Additionally, Western blot results showed that morin reduced the phosphokinase GSK3β activity and elevated the phosphatase PP2A activity, which led to lower tau phosphorylation. Morin reduced Aβ deposition and protected the synapse integrity, which might be the possible mechanism of protecting cognitive functions in septic mice. In conclusion, we identified that morin exerted anti-inflammation and anti-neurodegeneration effects in septic mice, and prevented further cognitive impairments.
Insights
Morin, a natural compound, reversed cognitive dysfunction and depressive behaviors in mice with sepsis-associated encephalopathy (SAE). It reduced inflammation and neurodegeneration, offering potential protection against SAE-induced cognitive impairments.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Sepsis-associated encephalopathy (SAE) causes long-term cognitive deficits in survivors.
- The complex pathological mechanisms of SAE remain incompletely understood.
- Morin, a flavone, possesses known neuroprotective and anti-inflammatory properties.
Purpose of the Study:
- To investigate the therapeutic potential of morin in a mouse model of sepsis-associated encephalopathy.
- To elucidate the underlying mechanisms of morin's neuroprotective effects in SAE.
Main Methods:
- Sepsis-associated encephalopathy was induced in mice using the cecal ligation and puncture (CLP) model.
- Morin was administered to treat septic mice.
- Cognitive function and depressive-like behaviors were assessed using novel object recognition and tail suspension tests.
- Serum cytokine levels (IL-6, MCP-1, TNF-α, IL-10) and microglial activation were measured.
- Western blot analysis was used to evaluate GSK3β, PP2A, tau phosphorylation, Aβ deposition, and synapse integrity.
Main Results:
- Morin treatment significantly reversed cognitive dysfunction and reduced depressive-like behaviors in septic mice.
- Morin administration down-regulated pro-inflammatory cytokines (IL-6, MCP-1, TNF-α) and modulated IL-10 levels.
- Morin diminished microglial activation, reduced GSK3β activity, increased PP2A activity, and decreased tau phosphorylation.
- Morin reduced amyloid-beta (Aβ) deposition and preserved synapse integrity in septic mice.
Conclusions:
- Morin demonstrates significant anti-inflammatory and anti-neurodegenerative effects in the context of SAE.
- Morin treatment effectively prevented cognitive impairments in septic mice, likely through mechanisms involving reduced neuroinflammation, tau pathology, and Aβ deposition.
- Morin represents a promising therapeutic candidate for mitigating cognitive deficits associated with sepsis-associated encephalopathy.

