Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor | Department of Rehabilitation Sciences | en_US |
| dc.contributor.advisor | Yau, Suk-yu Sonata (RS) | en_US |
| dc.contributor.advisor | Chiou, Amber (FSN) | en_US |
| dc.contributor.advisor | Mok, Daniel (FSN) | en_US |
| dc.creator | Hussain, Akhlaq | - |
| dc.identifier.uri | https://theses.lib.polyu.edu.hk/handle/200/14576 | - |
| dc.language | English | en_US |
| dc.publisher | Hong Kong Polytechnic University | en_US |
| dc.rights | All rights reserved | en_US |
| dc.title | Investigation of mechanisms underlying cognitive impairment induced by chronic exposure to air pollutant particulate matter 2.5 (PM2.5) in a mouse model | en_US |
| dcterms.abstract | Background | en_US |
| dcterms.abstract | Air pollution, particularly exposure to fine particulate matter (PM2.5), has emerged as a major environmental risk factor for brain health, contributing to increased susceptibility to neurodegenerative diseases. While PM2.5 is known to cross the blood-brain barrier and induce oxidative stress, recent evidence suggests that its impact on the gut-brain axis (GBA) may be crucial in mediating neurological dysfunction. However, the mechanisms by which PM2.5-induced alterations in the gut microbiota and its metabolites contribute to brain pathology remain poorly understood. | en_US |
| dcterms.abstract | Research Question | en_US |
| dcterms.abstract | Does chronic PM2.5 exposure impair brain function through alterations in the gut microbiota and its metabolites, and can plant-derived compounds mitigate these effects? | en_US |
| dcterms.abstract | Hypothesis | en_US |
| dcterms.abstract | It is hypothesized that PM2.5 exposure induces gut dysbiosis and increases the production of the pro-inflammatory metabolite trimethylamine-N-oxide (TMAO), which, in turn, promotes hippocampal impairment via oxidative stress and endoplasmic reticulum (ER) stress. Furthermore, dietary interventions with resveratrol (RSV) or Lycium barbarum glycopeptide (LbGP), which can reduce oxidative stress or 1% 3,3-dimethyl-1-butanol (DMB), which can suppress TMAO production by the liver, attenuate these adverse effects. | en_US |
| dcterms.abstract | Methodology | en_US |
| dcterms.abstract | To address these questions, a well-established mouse model using male and female C57BL/6J mice was employed. Animals were intratracheally exposed to roadside traffic pollutant PM2.5 (2.5 μg/μL suspended in artificial lung fluid) three times per week for three weeks. Intervention groups received either a 0.4% RSV-enriched diet, LbGP in drinking water (100mg/kg), or 1% DMB, whereas the PM2.5-only group received no treatment,, and the control group received only artificial lung fluid. Behavioral assessments were conducted to evaluate working and spatial memory, as well as anxiety- and depressive-like behaviors. Molecular and electrophysiological analyses were performed to assess gut microbiota composition, TMAO levels in serum and hippocampus, neurogenesis, synaptic plasticity in the dentate gyrus, and the expression of synaptic proteins and ER stress markers. | en_US |
| dcterms.abstract | Key Findings | en_US |
| dcterms.abstract | Chronic PM2.5 exposure resulted in significant impairments in working and spatial memory, increased anxiety- and depressive-like behaviors, and greater vulnerability in female mice. These behavioral deficits were accompanied by dysbiosis of the gut microbiota, elevated TMAO levels, reduced adult neurogenesis, impaired synaptic plasticity, and altered expression of synaptic proteins (PSD-95, synaptophysin) and ER stress markers in the hippocampus. Notably, DMB treatment effectively reduced TMAO levels and reversed many of the cognitive, molecular, and electrophysiological impairments, supporting a causal role for TMAO in PM2.5-induced neurotoxicity. Both RSV and LbGP also conferred neuroprotective effects: RSV broadly improved behavioral and molecular outcomes, while LbGP was particularly effective in reducing depressive-like behaviors and ER stress. | en_US |
| dcterms.abstract | Significance | en_US |
| dcterms.abstract | The findings demonstrate that the gut microbiota-TMAO-ER stress axis is a key mechanism linking PM2.5 exposure to hippocampal dysfunction and cognitive impairment. Importantly, the findings suggest that plant-derived dietary compounds may provide safe and accessible strategies for protecting against air-pollution-induced neurotoxicity. These insights advance our understanding of the gut-brain axis in environmental neurotoxicity and highlight novel intervention targets for mitigating the adverse neurological effects of air pollution. | en_US |
| dcterms.extent | xxii, 196 pages : color illustrations | en_US |
| dcterms.isPartOf | PolyU Electronic Theses | en_US |
| dcterms.issued | 2026 | en_US |
| dcterms.educationalLevel | Ph.D. | en_US |
| dcterms.educationalLevel | All Doctorate | en_US |
| dcterms.accessRights | open access | en_US |
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