2. Academic Validation
  3. Inactivation of microglia dampens blood-brain barrier permeability and loss of dopaminergic neurons in paraquat-lesioned mice

Inactivation of microglia dampens blood-brain barrier permeability and loss of dopaminergic neurons in paraquat-lesioned mice

  • Food Chem Toxicol. 2023 Feb 24;113692. doi: 10.1016/j.fct.2023.113692.
Yu-Ting Zhou 1,  Ya-Ning Xu 1,  Xi-Yun Ren 2,  Xiao-Feng Zhang 3
Affiliations

Affiliations

  • 1 Department of Toxicology, Public Health School, Harbin Medical University, No 157, Baojian Road, Nangang District, Heilongjiang Province, Harbin, 150081, China.
  • 2 Experimental Center for Preventive Medicine Teaching, Public Health School, Harbin Medical University, No 157, Baojian Road, Nangang District, Heilongjiang Province, Harbin, 150081, China.
  • 3 Department of Toxicology, Public Health School, Harbin Medical University, No 157, Baojian Road, Nangang District, Heilongjiang Province, Harbin, 150081, China. Electronic address: [email protected].
PMID: 36842752 DOI: 10.1016/j.fct.2023.113692
Abstract

Prior studies indicated the involvement of neuroinflammation in the dopaminergic neurodegeneration in mice of paraquat (PQ)-induced Parkinson's disease (PD), but the underlying mechanisms remain to be elucidated. The present study explored whether microglia-mediated inflammation disrupted blood-brain barrier (BBB) and its related mechanism. C57BL/6 mice were injected intraperitoneally with PQ, twice a week for six weeks, following with or without minocycline (intraperitoneal injection, once every two days). The microglial activation, BBB permeability, expression of tight junctions (TJs) proteins and matrix metalloproteinase (MMP), as well as the loss of dopaminergic neurons and neurological deficits assessment, were evaluated. Minocycline efficiently restrained nigral microglial activation induced by PQ in mice. PQ-induced increase of EB content in the brain and excessive expression of zonula occludin-1 (ZO-1), claudin-5 and occludin were significantly dampened by minocycline treatment. Inhibition of microglial activation by minocycline greatly ameliorated the loss of dopaminergic neurons and neurological dysfunctions in PQ-exposed mice. Also, microglial inactivation downregulated the expression of MMP-2/9 in PQ-lesioned mice. These findings suggested the potential protection of suppressing microglia-mediated neuroinflammation against dopaminergic neurodegeneration through attenuating BBB disruption in a mouse of PQ-induced PD, and MMP-2/9 might involve in the contribution, which needs to be verified in future study.

Keywords

Blood-brain barrier; Dopaminergic neurons; Matrix metalloproteinases; Microglial inactivation; Paraquat; Tight junctions.

Figures
Products