Pork Combustion Particulate Matter Exacerbates Cognitive Impairment by Accelerating Amyloid-β Accumulation in 5× FAD Mice

Abstract

Particulate matter (PM), a key component of air pollution, is globally associated with adverse health effects, including premature mortality. Although the majority of the human lifespan is spent indoors, knowledge on the effects of indoor exposure to aerosol particles remains limited. Therefore, we aimed to investigate the effects of exposure to PM2.5 (<= 2.5 mu m) generated during indoor cooking on Alzheimer's disease (AD). To investigate the signaling pathways activated by pork combustion PM2.5 (PC-PM2.5), 2-month-old 5 & times; FAD mice were exposed to whole-body inhalation five times a week for 1 month. PC-PM2.5-exposed mice were evaluated using the airway hyperresponsiveness test, novel object location recognition (NLR) task, and Y-maze task, and glial cell localization was observed in the hippocampal brain regions. Additionally, cognition-related markers (BDNF and CREB), amyloid beta (A beta) accumulation, pro-inflammatory response, post-synapse 95 (PSD95), and Wnt/GSK3 beta signaling pathway expression were measured in hippocampal lysates to evaluate pathological changes. PC-PM2.5 treatment considerably increased A beta accumulation and airway hyperresponsiveness and decreased cognitive function in 5 & times; FAD mice. PC-PM2.5 treatment accelerated A beta accumulation and pro-inflammatory cytokine expression, as well as GFAP+ localization, and reduced cognition-related markers and synaptic plasticity in the hippocampus. Additionally, in the PC-PM2.5-treated group, Wnt expression was lower than that in 5 & times; FAD mice, GSK3 beta phosphorylation increased, and nuclear translocation of beta-catenin decreased. Therefore, this study confirmed that exposure to PC-PM2.5, which is common in daily life, accelerates cognitive decline as a risk factor for AD and suggests that regulating the Wnt/GSK3 beta/beta-catenin pathway may be a potential prevention strategy. In summary, this study elucidates the changes and molecular signaling pathways activated by PM exposure and provides insights into the mechanistic links between air pollution and neurodegenerative diseases such as AD.