PM2.5 triggers tau aggregation in a mouse model of tauopathy
Congcong Liu, Lanxia Meng, Yan Gao, Jiehui Chen, Min Zhu, Min Xiong, Tingting Xiao, Xiaoling Gu, Chaoyang Liu, Tao Li, Zhentao Zhang
Congcong Liu, Lanxia Meng, Yan Gao, Jiehui Chen, Min Zhu, Min Xiong, Tingting Xiao, Xiaoling Gu, Chaoyang Liu, Tao Li, Zhentao Zhang
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Research Article Neuroscience

PM2.5 triggers tau aggregation in a mouse model of tauopathy

Abstract

The aggregation and prion-like propagation of tau are the hallmarks of Alzheimer’s disease (AD) and other tauopathies. However, the molecular mechanisms underlying the assembly and spread of tau pathology remain elusive. Epidemiological data show that exposure to fine particulate matter (PM2.5) is associated with an increased risk of AD. However, the molecular mechanisms remain unknown. Here, we showed that PM2.5 triggered the aggregation of tau and promoted the formation of tau fibrils. Injection of PM2.5-induced tau preformed fibrils (PFFs) into the hippocampus of tau P301S transgenic mice promoted the aggregation of tau and induced cognitive deficits and synaptic dysfunction. Furthermore, intranasal administration of PM2.5 exacerbated tau pathology and induced cognitive impairment in tau P301S mice. In conclusion, our results indicated that PM2.5 exposure promoted tau pathology and induced cognitive impairments. These results provide mechanistic insight into how PM2.5 increases the risk of AD.

Authors

Congcong Liu, Lanxia Meng, Yan Gao, Jiehui Chen, Min Zhu, Min Xiong, Tingting Xiao, Xiaoling Gu, Chaoyang Liu, Tao Li, Zhentao Zhang

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Figure 4

PM2.5-tau PFFs induce cognitive impairment and synaptic dysfunction in tau P301S mice.

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PM2.5-tau PFFs induce cognitive impairment and synaptic dysfunction in t...
(A–D) The spatial learning memory of mice injected with PBS, tau PFFs, or PM2.5-tau PFFs was assessed by the Morris water maze test. Shown are the escape latency during training (A), the escape latency on day 5 (B), the time spent in the target quadrant in the probe trial (C), and the swim speed (D) of mice injected with PBS, pure tau PFFs, or PM2.5-tau PFFs. n = 8 mice per group. (E) The spatial working memory of mice injected with PBS, tau PFFs, or PM2.5-tau PFFs was assessed by the Y-maze test. Shown is the time spent in the new arm. n = 8 mice per group. (F–H) Representative images of synapses in the hippocampus of mice injected with PBS, pure tau PFFs, or PM2.5-tau PFFs (scale bars, 1 μm). Quantification of synapse clefts (G) and postsynaptic density (PSD) (H). n = 7 mice per group (each point represents the average of 10 random fields from each mouse). (I and J) Representative images of Golgi staining of the dendritic spines in the hippocampal area. (J) Quantification of spine density. n = 7 mice per group (each point represents the average of 10 random fields from each mouse). Scale bars, 20 μm. (K and L) The amplitude of fEPSPs after HFS recorded in hippocampal slices. (K) Shown traces are representative fEPSPs of 7 samples recorded before and after LTP induction. (L) Quantitative analysis of normalized fEPSPs 50–60 minutes after HFS. n = 7 mice per group. Data are presented as mean ± SEM. P values were determined by 1-way ANOVA followed by Tukey’s multiple comparisons test.