Association between PM2.5 exposure by inhalation and brain damages of Alzheimer’s disease in transgenic mice

Title

Association between PM_2.5 exposure by inhalation and brain damages of Alzheimer’s disease in transgenic mice

 Pengfei Fu ^a,b,

Corresponding author^⁎: Ken Kin Lam Yung ^{a,b, ⁎} (kklyung@hkbu.edu.hk)

a Department of Biology, Hong Kong Baptist University, Hong Kong SAR, China.

b Golden Meditech Center for NeuroRegeneration Sciences

 

ABSTRACT

Background: Fine particulate matter (PM_2.5) exposure increases the risk of neurological disorders. However, the relevance between PM_2.5 and Alzheimer’s disease (AD) needs to be identified and the effect of PM_2.5 exposure on the brain in AD mice remains unclear.

Objective: To assess the effects of PM_2.5 exposure on AD and investigate the brain damage in AD transgenic mice exposed to PM_2.5.

Methods: We searched articles from the database of PubMed for meta-analyses on the association between PM_2.5 exposure and AD. Further, using a novel real-world whole-body inhalation exposure system, wild type (WT) and APP/PS1 transgenic mice (AD mice) were respectively exposed to filtered air (FA) or ambient PM_2.5 for 8 weeks in Taiyuan, China. The pathological and ultrastructural changes and levels of Aβ-42, TNF-α, and IL-6 in brains in FA-WT mice, FA-AD mice, FA-PM_2.5 mice, and PM_2.5-AD mice were measured.

Results: Long-term PM_2.5 exposure had the association with increased risks of dementia and AD by OR of 1.16 (95% CI 1.07–1.26) and 3.26 (95% CI 0.84–12.74) via meta-analysis. Both lightly- and heavily polluted countries showed such increased risks. In the open field test, the PM_2.5-AD mice showed more significant degenerative symptoms of AD by the behavioral change in movement. Hematoxylin-eosin staining results showed that noticeable histopathological injury such as structural disorder, hyperemia, and sporadic inflammatory cell infiltration in the brain of PM_2.5-AD mice, and transmission electron microscope results displayed that serious damage in the brain in PM_2.5-AD mice, which maintained disorder of cristae and vacuolation of mitochondria, synaptic abnormalities, and loose myelin sheaths. Aβ-42, TNF-α and IL-6 levels in brains of PM_2.5-AD mice had raised more strongly than that of FA-WT or FA-AD mice.

Conclusion: This study indicated a strong association between PM_2.5 exposure and AD risks. PM_2.5 significantly aggravated the severity of neuronal pathomorphological changes and inflammation in AD mice when Aβ-42 levels in the brain were visibly increased.

 

Acknowledgment:

Car-SCs Treatment Technology and Study the Application of Inorganic Nanomatrices on MSC T-cells Proliferation (Project Ref: RMGS-2019-1-03).