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TREM2 mitigates NLRP3-mediated neuroinflammation through the NF-κB and PI3k/Akt signaling pathways in juvenile rats exposed to ambient particulate matter

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Abstract

Ambient particulate matter (PM) is a global public and environmental problem. PM is closely associated with several neurological disorders that typically involve neuroinflammation. There have been few studies on the effect of PM on neuroinflammation to date. In this study, we used a juvenile rat model (PM exposure was conducted at a dose of 10 mg/kg body weight per day for 4 weeks) and a BV-2 cell model (PM exposure was conducted at concentrations of 50, 100, 150, and 200 μg/ml for 24 h) to investigate PM-induced neuroinflammation mediated by NLRP3 inflammasome activation and the role of TREM2 in this process. Our findings revealed that PM exposure reduced TREM2 protein and mRNA levels in the rat hippocampus and BV-2 cells. TREM2 overexpression attenuated PM-induced spatial learning and memory deficits in rats. Moreover, we observed that TREM2 overexpression in vivo and in vitro effectively mitigated the increase in NLRP3 and pro-Caspase1 protein expression, as well as the secretion of IL-1β and IL-18. Exposure to PM increased the expression of NF-κB and decreased the phosphorylation of PI3k/Akt in vivo and in vitro, and this process was effectively reversed by overexpressing TREM2. Our results indicated that PM exposure could reduce TREM2 expression and induce NLRP3 inflammasome-mediated neuroinflammation and that TREM2 could mitigate NLRP3 inflammasome-mediated neuroinflammation by regulating the NF-κB and PI3k/Akt signaling pathways. These findings shed light on PM-induced neuroinflammation mechanisms and potential intervention targets.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

PM:

Ambient particulate matter

GBD:

Global burden of disease

CNS:

Central nervous system

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

ASC:

Apoptosis-associated speck-like protein

pro-IL-1β:

Pro-interleukin-1β

TREM2:

Triggering receptor expressed on myeloid cells 2

Aβ:

β-Amyloid protein

AAV:

Adeno-associated virus

CCK8:

Cell counting kit-8

SD:

Sprague Dawley

PND:

Postnatal day

NOR:

Novel object recognition test

MWM:

Morris water maze test

RT-qPCR:

Quantitative real-time polymerase chain reaction

Ct:

Cycle threshold

ELISA:

Enzyme-Linked Immunosorbent Assay

SEM:

Standard errors of the means

BBB:

Blood-brain barrier

MMC:

Metropolitan Mexico City

ASD:

Autism spectrum disorder

ADHD:

Attention deficit hyperactivity disorder

TNF-α:

Tumor necrosis factor-α

IκB:

NF-κB inhibitors

EMSA:

Electrophoretic mobility shift assay

ChIP:

Chromatin immunoprecipitation

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Funding

This work was supported by the Talent Program of Chongqing, China (cstc2021ycjh-bgzxm0187) and the Chongqing Postdoctoral Special Foundation (CSTB2022NSCQ-BHX0708).

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Authors and Affiliations

  1. Department of Neurology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children’s Hospital of Chongqing Medical University, No. 136, Zhongshan Er Road, Yuzhong District, Chongqing, 400014, China

    Jianxiong Gui, Jie Liu, Lingman Wang, Hanyu Luo, Dishu Huang, Xiaoyue Yang, Honghong Song, Ziyao Han, Ran Ding, Jiaxin Yang & Li Jiang

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  1. Jianxiong Gui
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  2. Jie Liu
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  11. Li Jiang
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Jianxiong Gui, Li Jiang, Jie Liu, Lingman Wang, Hanyu Luo, and Ziyao Han. The first draft of the manuscript was written by Jianxiong Gui, Li Jiang, Dishu Huang, Xiaoyue Yang, Honghong Song, Ran Ding, and Jiaxin Yang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Li Jiang.

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Ethical approval

All animal experimental procedures conducted in our study adhered to the guidelines set forth by the National Research Council’s Guide for the Care and Use of Laboratory Animals. Furthermore, these procedures were thoroughly reviewed and approved by the Ethics Committee of the Children’s Hospital Affiliated with Chongqing Medical University, under Protocol No. CHCMU-IACUC20220629008.

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Gui, J., Liu, J., Wang, L. et al. TREM2 mitigates NLRP3-mediated neuroinflammation through the NF-κB and PI3k/Akt signaling pathways in juvenile rats exposed to ambient particulate matter. Environ Sci Pollut Res 30, 119863–119878 (2023). https://doi.org/10.1007/s11356-023-30764-6

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