Blood-brain barrier disruption and inflammation reaction in mice after chronic exposure to Microcystin-LR

Jing Wang; Changliang Zhang; Jinling Zhu; Jie Ding; Yabing Chen; Xiaodong Han

doi:10.1016/j.scitotenv.2019.06.387

Blood-brain barrier disruption and inflammation reaction in mice after chronic exposure to Microcystin-LR

Sci Total Environ. 2019 Nov 1:689:662-678. doi: 10.1016/j.scitotenv.2019.06.387. Epub 2019 Jun 26.

Authors

Jing Wang¹, Changliang Zhang¹, Jinling Zhu¹, Jie Ding¹, Yabing Chen², Xiaodong Han³

Affiliations

¹ Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, China; State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China.
² Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, China; State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China. Electronic address: ybchen916218@126.com.
³ Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, China; State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China. Electronic address: hanxd@nju.edu.cn.

PMID: 31279213
DOI: 10.1016/j.scitotenv.2019.06.387

Abstract

Microcystin-leucine-arginine (MC-LR), which produced by toxic cyanobacteria and widely present in eutrophic waters, has been shown to have potent acute hepatotoxicity. MC-LR has been revealed to inflict damage to brain, while the neurotoxicity of chronic exposure to MC-LR and mechanisms underlying it are still confusing. Here, the mice were exposed to MC-LR dissolved in drinking water at dose of 1, 7.5, 15, and 30 μg/L for consecutive 180 days. MC-LR accumulated in mouse brains and impaired the blood-brain barrier by inducing the expression of matrix metalloproteinase-8 (MMP-8), which was regulated by NF-κB, c-Fos and c-Jun. Furthermore, MC-LR exposure induced microglial and astrocyte activation and resultant neuroinflammatory response. This study highlights the risks to human health of the current microcystin exposure.

Keywords: Blood-brain barrier disruption; Inflammation; Microcystin-LR; Neurotoxicity.

MeSH terms

Animals
Astrocytes / drug effects
Astrocytes / physiology
Blood-Brain Barrier / drug effects*
Gene Expression / drug effects
Inflammation / chemically induced
Inflammation / physiopathology*
Male
Marine Toxins
Mice
Mice, Inbred BALB C
Microcystins / toxicity*
Microglia / drug effects
Microglia / physiology
Tight Junctions / drug effects*
Tight Junctions / metabolism

Substances

Marine Toxins
Microcystins
cyanoginosin LR