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Updated: Nov 1, 2025

Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity
Published on: October 25, 2016
Effects of lead exposure on the activation of microglia in mice fed with high-fat diets
Lei Wu1, Shuang Li2, Shulan Pang1
1School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China.
Abstract:
Lead (Pb) exposure can cause central nervous system (CNS) damage. The process of Pb neurotoxicity is accompanied by the microglia activation. In addition, microglia activation was observed under the intervention of high-fat diets (HFD). This study was designed to investigate the effect of Pb on the cognitive function of mice with HFD, with focus on the microglia activation in brain. Male C57BL/6J mice, 8 weeks of age, were randomly divided into control, HFD, Pb, and HFD + Pb groups. The results showed that HFD following Pb exposure could exacerbate the learning and memory impairment in mice. Pb exposure could promote microglia activation and increase the expression of M1 microglia marker and decrease the expression of M2 microglia marker in the hippocampus of mice with HFD. Our finding suggested that Pb exposure may aggravate CNS damage by promoting M1 polarization and inhibiting M2 polarization of hippocampal microglia in HFD mice.
Insights
High-fat diets combined with lead (Pb) exposure worsen cognitive deficits and central nervous system (CNS) damage in mice. This occurs by promoting M1 microglia activation and inhibiting M2 polarization in the hippocampus.
Area of Science:
- Neuroscience
- Toxicology
- Immunology
Background:
- Lead (Pb) exposure is a known neurotoxin causing central nervous system (CNS) damage.
- Microglia activation is implicated in Pb neurotoxicity and is also observed with high-fat diets (HFD).
Purpose of the Study:
- To investigate the combined effects of Pb exposure and HFD on cognitive function in mice.
- To examine the role of microglia activation in the hippocampus under these conditions.
Main Methods:
- Male C57BL/6J mice were divided into four groups: control, HFD, Pb exposure, and HFD + Pb exposure.
- Cognitive function, learning, and memory were assessed.
- Microglia activation markers (M1 and M2) in the hippocampus were analyzed.
Main Results:
- HFD exacerbated Pb-induced learning and memory impairments.
- Pb exposure promoted microglia activation in the hippocampus of HFD mice.
- Pb exposure increased M1 microglia markers and decreased M2 microglia markers.
Conclusions:
- Combined HFD and Pb exposure worsen cognitive deficits and CNS damage.
- Pb exposure aggravates CNS damage by skewing hippocampal microglia towards an M1 pro-inflammatory phenotype and away from an M2 anti-inflammatory phenotype in HFD mice.
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