Neuropathology changed by 3- and 6-months low-level PM2.5 inhalation exposure in spontaneously hypertensive rats

Chuang, Hsiao-Chi; Chen, Hsin‐Chang; Chai, Pei-Jui; Liao, Hsin‐Tzu; Wu, Chang‐Fu; Chen, Chia-Ling; Jhan, Ming-Kai; Hsieh, Hui-I; K, Wu; Chen, Ta‐Fu; Cheng, Tsun‐Jen

doi:10.1186/s12989-020-00388-6

Cited by 23 publications

(16 citation statements)

References 75 publications

(95 reference statements)

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“…The mean concentration of PM 2.5 was 11.38 μg/m 3 during the entire exposure period in the present study, which was near the WHO guidelines and similar to our previous studies [ 22 , 32 , 33 ]. The composition analysis of our collected PM 2.5 showed that SO 4 2- , NH 4 + , and NO 3 - were the enriched ions, which originate from urban traffic or coal burning [ 34 ].…”

Section: Discussionsupporting

confidence: 92%

“…The accumulation of pathological proteins and the related neuronal dysfunction in the olfactory bulb were associated with the occurrence of neuropathology in other brain areas, which may be used an early biomarker for AD and other neurodegenerative diseases [ 57 ]. Our previous studies also showed the elevated p-tau expression in the olfactory bulb of spontaneously hypertensive rats subchronic exposed to low-level PM 2.5 [ 32 ].…”

Section: Discussionmentioning

confidence: 90%

“…These results revealed that autophagy activation, neuron histological changes, and increased oxidative stress and neuroinflammation were observed in rats after chronic exposure of PM. Additional results also showed that even low concentration (range 8.6~16.3 μg/m 3 ) exposure to PM caused brain impairment in wild-type mice (unpublished data) and spontaneously hypertensive rats [ 32 , 33 ]. However, data of neuronal toxicity and AD-related disease progression after PM 2.5 exposure in AD transgenic mouse models were limited.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies revealed negative performances in MWM [ 43 , 44 ], Barnes maze task, force swimming [ 45 ], and novel object recognition (NOR) test [ 46 ] in rodent models after subchronic or chronic exposure to higher concentrations of PM. However, no obvious behavioral differences in the MWM [ 32 , 47 ], Y maze, force swimming [ 38 ], or rotarod test [ 28 ] were found in rodents under relatively lower concentration exposure to PM. Therefore, a low dose of PM 2.5 may not cause severe clinical cognitive or motor decline.…”

Section: Discussionmentioning

confidence: 99%

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Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer’s disease mouse model

et al. 2021

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Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM2.5) exposure and Alzheimer’s disease (AD), the PM2.5-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM2.5 via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM2.5 for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM2.5 exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM2.5 induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM2.5 exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM2.5 subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM2.5 after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM2.5-mediated development of AD.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer’s disease mouse model

et al. 2021

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“…The characteristic uid markers of AD, decreased Aβ42 and increased P-tau protein levels in cerebrospinal uid (CSF), were also reported in urbanites with high exposure to PM 2.5 [11]. Accelerated amyloid plaque deposition and P-tau accumulation have been detected in the brains of animal models after exposure to concentrated air pollutants, especially in the hippocampal area [17,18,19,20,21]. The successive pathways of in ammation, oxidative stress, microglial activation, and even DNA damage are thought to cause this degenerative pathology [17,19,22,23,24].…”

Section: Introductionmentioning

confidence: 98%

White Matter Pathology in Alzheimer’s Transgenic Mice With Chronic Exposure to Low-Level Ambient Fine Particulate Matter

Chen

Lee

Zheng

et al. 2021

Preprint

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Background: Air pollution, especially fine particulate matter (PM), can cause brain damage, cognitive decline, and an increased risk of neurodegenerative disease, especially Alzheimer’s disease (AD). Typical pathological findings of amyloid and tau protein accumulation have been detected in the brain after exposure in animal studies. However, these observations were based on high levels of PM exposure, which were far from the WHO guidelines and those present in our environment. In addition, white matter involvement by air pollution has been less reported. Thus, this experiment was designed to simulate the true human world and to discuss the possible white matter pathology caused by air pollution. Results: 6-month-old female 3xTg-AD mice were divided into exposure and control groups and housed in the Taipei Air Pollutant Exposure System (TAPES) for 5 months. The mice were subjected to the Morris water maze test after exposure and were then sacrificed with brain dissection for further analyses. The mean mass concentration of PM2.5 during the exposure period was 13.85 μg/m3. After exposure, there was no difference in spatial learning function between the two groups, but there was significant decay of memory in the exposure group. Significantly decreased total brain volume and more neuronal death in the cerebral and entorhinal cortex and demyelination of the corpus callosum were noted by histopathological staining after exposure. However, there was no difference in the accumulation of amyloid or tau on immunohistochemistry staining. For the protein analysis, amyloid was detected at significantly higher levels in the cerebral cortex, with lower expression of myelin basic protein in the white matter. A diffuse tensor image study also revealed insults in multiple white matter tracts, including the optic tract. Conclusions: In conclusion, this pilot study showed that even chronic exposure to low PM2.5 concentrations still caused brain damage, such as gross brain atrophy, cortical neuron damage, and multiple white matter tract damage. Typical amyloid cascade pathology did not appear prominently in the vulnerable brain region after exposure. These findings imply that multiple pathogenic pathways induce brain injury by air pollution, and the optic nerve is another direct invasion route in addition to olfactory nerve.

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An Air Particulate Pollutant Induces Neuroinflammation and Neurodegeneration in Human Brain Models

et al. 2021

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Fine particulate matter (PM2.5), a major component among air pollutants, highlights as a global health concern. Several epidemiological studies show the correlation between chronical PM2.5 exposure and incidents of neurological disorders including Alzheimer's disease. However, the mechanisms have not been well understood, partly due to the lack of model systems that reflect the physiologically relevant innate immunity in human brains. Here, PM2.5‐polluted human brain models (PMBs) are created in a 3D microfluidic platform reconstituting key aspects of human brain immunity under the PM2.5 exposure. PM2.5 penetration across a blood–brain barrier (BBB) model and accumulation in the brain tissue side of the model are first validated. Second, the PMB model shows that the BBB‐penetrating PM2.5 initiates astrogliosis, resulting in slight neuronal loss and microglial infiltration. Third, it is demonstrated that the infiltrating microglia obtain M1 phenotype induced by interleukin‐1β and interferon‐γ from neurons and reactive astrocytes under the PM2.5 exposure. Finally, it is observed that additional proinflammatory mediators and nitric oxide released from the M1 microglia exacerbate neuronal damages, such as synaptic impairment, phosphoric tau accumulation, and neuronal death. This study suggests that PM2.5 can be a potential environmental risk factor for dementia mediated by the detrimental neuroinflammation.

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Neuropathology changed by 3- and 6-months low-level PM2.5 inhalation exposure in spontaneously hypertensive rats

Cited by 23 publications

References 75 publications

Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer’s disease mouse model

Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer’s disease mouse model

White Matter Pathology in Alzheimer’s Transgenic Mice With Chronic Exposure to Low-Level Ambient Fine Particulate Matter

An Air Particulate Pollutant Induces Neuroinflammation and Neurodegeneration in Human Brain Models

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