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Published on: May 15, 2019
Lipopolysaccharide exacerbates depressive-like behaviors in obese rats through complement C1q-mediated synaptic
Titikorn Chunchai1,2, Thirathada Chinchapo1,2,3, Jirapas Sripetchwandee1,2,3
1Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Insights
High-fat diets and LPS worsen brain inflammation and depressive behaviors. Combined, they exacerbate metabolic issues, neuroinflammation, and synaptic loss, impacting cognition and mood.
Area of Science:
- Neuroscience
- Metabolic Syndrome
- Neuroinflammation
Background:
- Prolonged high-fat diet (HFD) consumption impairs cognition and mood.
- The combined impact of HFD and lipopolysaccharide (LPS) on brain health is understudied.
Purpose of the Study:
- Investigate HFD and LPS effects on microglial function, synaptic integrity, cognition, and behavior.
- Determine combined effects on neuroinflammation, metabolic disturbances, and brain metabolism.
Main Methods:
- Rats fed normal diet (ND) or HFD for 12 weeks, followed by vehicle or LPS injection.
- Assessed cognitive function, depressive behaviors, and collected brain/spleen tissues.
- Utilized western blot, qRT-PCR, immunofluorescence, and metabolomics for analysis.
Main Results:
- HFD induced obesity, oxidative stress, and blood-brain barrier disruption.
- Both HFD and LPS increased neuroinflammation and synaptic loss, exacerbated by combination.
- HFD caused cognitive decline; both HFD and LPS induced depressive behaviors, worsened by combination.
Conclusions:
- LPS exacerbates metabolic disturbances, neuroinflammation, and microglial synaptic engulfment in obese rats.
- Combined HFD and LPS significantly worsen neuroinflammation and depressive behaviors.
Aim:
Prolonged high-fat diet (HFD) consumption has been shown to impair cognition and depression. The combined effects of HFD and lipopolysaccharide (LPS) administration on those outcomes have never been thoroughly investigated. This study investigated the effects of LPS, HFD consumption, and a combination of both conditions on microglial dysfunction, microglial morphological alterations, synaptic loss, cognitive dysfunction, and depressive-like behaviors.
Methods:
Sixty-four male Wistar rats were fed either a normal diet (ND) or HFD for 12 weeks, followed by single dose-subcutaneous injection of either vehicle or LPS. Then, cognitive function and depressive-like behaviors were assessed. Then, rats were euthanized, and the whole brain, hippocampus, and spleen were collected for further investigation, including western blot analysis, qRT-PCR, immunofluorescence staining, and brain metabolome determination.
Results:
HFD-fed rats developed obese characteristics. Both HFD-fed rats with vehicle and ND-fed rats with LPS increased cholesterol and serum LPS levels, which were exacerbated in HFD-fed rats with LPS. HFD consumption, but not LPS injection, caused oxidative stress, blood-brain barrier disruption, and decreased neurogenesis. Both HFD and LPS administration triggered an increase in inflammatory genes on microglia and astrocytes, increased c1q colocalization with microglia, and increased dendritic spine loss, which were exacerbated in the combined conditions. Both HFD and LPS altered neurotransmitters and disrupted brain metabolism. Interestingly, HFD consumption, but not LPS, induced cognitive decline, whereas both conditions individually induced depressive-like behaviors, which were exacerbated in the combined conditions.
Conclusions:
Our findings suggest that LPS aggravates metabolic disturbances, neuroinflammation, microglial synaptic engulfment, and depressive-like behaviors in obese rats.
