Abstract
PM2.5-related neurological and mental diseases, such as cognitive impairment and stroke, tend to cause disability. Six-week-old male C57BL/6 mice were divided into 6 groups and exposed to concentrated PM2.5 or filtered air for 2, 4, and 6 months, respectively. The neurobehavioral changes of mice were tested. The weight of the whole brain and olfactory bulbs were recorded at the end of exposure, and the brain structure was observed by hematoxylin and eosin (HE) staining. Serum indicators, mRNA, and protein expressions were detected. The spatial learning memory ability was impaired, and the mice were more anxious after PM2.5 exposure. Relative brain weight decreased with age, and PM2.5 exposure exceeded the decrease of relative brain weight. Interestingly, superoxide dismutase (SOD) and albumin decreased in the PM2.5-exposed groups although neuronal morphology and other serum indicators did not show significant difference between PM and FA groups. Moreover, PM2.5 induced the increase of plasminogen at 2 months but recovered at 4 months and then increased at 6 months again. The results from protein expression and transcriptomic test demonstrated that PI3K/AKT/FoxO1 pathway might be activated after 6-month PM2.5 exposure in mice. Indicators albumin, the percentage of albumin over IgG (A/G value), and plasminogen were the main serous changes in mice after early-stage (2 months) and long-term (6 months) PM2.5 exposure. In addition, early-stage injury induced by PM2.5 might recover at later time point and display significant injury again with the exposure time. PM2.5 exposure-induced brain injury might be associated with the activation of PI3K/AKT/FoxO1 pathway.
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The data that support the findings of this study are available, but restrictions apply to the availability of these data. Data are however available from the authors upon reasonable request.
Abbreviations
- PM2.5 :
-
Fine particulate matter
- DALYs:
-
Disability-adjusted life years
- FA:
-
Filtered air
- SIR:
-
Systemic inflammatory response
- BDNF:
-
Brain-derived neurotrophic factor
- miRNA:
-
microRNA
- FoxO:
-
Forkhead box O
- PI3K:
-
Phosphatidylinositol 3-kinase
- Akt:
-
Protein kinase B
- NGF:
-
Nerve growth factor
- HSA:
-
Human serum albumin
- PAI-1:
-
Plasminogen activator inhibitor 1
- Shanghai-METAS:
-
Shanghai Meteorological and Environmental Animal Exposure System
- HE:
-
Hematoxylin and eosin
- FPKM:
-
Fragments per kilobase of exon per million mapped reads
- PCA:
-
Principal component analysis
- IL:
-
Interleukin
- TNF-α:
-
Tumor necrosis factor α
- SOD:
-
Superoxide dismutase
- ROS:
-
Reactive oxygen species
- RT-PCR:
-
Real-time PCR
- ANOVA:
-
One-way analysis of variance
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This study was financially supported by the National Key Research and Development Program of China (2017YFC0211602) and the National Natural Science Foundation of China (No. 81673125 and 91543119).
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LYS designed and performed the experiment and wrote the paper. KP performed the experiment and analyzed the data. XHD, SJ, XJZ, JZ, LL, DXF, ZXL, MDZ, and YWZ performed the experiment. JZ provide technical support of the exposure equipment. JZZ designed the experiment and revised the paper. All authors read and approved the final manuscript.
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The study was approved by the Fudan University Animal Care and Use Committee, and all animal procedures were treated in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. The approval number was 201902063S.
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Song, L., Pan, K., Du, X. et al. Ambient PM2.5-induced brain injury is associated with the activation of PI3K/AKT/FoxO1 pathway. Environ Sci Pollut Res 28, 68276–68287 (2021). https://doi.org/10.1007/s11356-021-15405-0
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DOI: https://doi.org/10.1007/s11356-021-15405-0