Ambient PM2.5 chronic exposure leads to cognitive decline in mice: From pulmonary to neuronal inflammation

Shou, Yikai; Zhu, Xiaoli; Zhu, Danna; Yin, Hongping; Shi, Yingying; Chen, Minyan; Lü, Linyuan; Qian, Qiwei; Zhao, Dongjiu; Hu, Yu; Wang, Huanhuan

doi:10.1016/j.toxlet.2020.06.014

Cited by 43 publications

(20 citation statements)

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“…Previously, we have reported that chronic PM 2.5 exposure led to cognitive decline in mice [5]. However, we found that neuroin ammation may only occur later than cognitive impairment in mice, the event earlier than behavior phenotype induced by PM 2.5 exposure and the underlying molecular mechanism remain unclear.…”

Section: Introductionmentioning

confidence: 74%

“…Children who are chronically exposed to PM 2.5 above the standards would suffer from obesity and cognitive de cits [21]. Recently, we have found that chronic PM 2.5 exposure for 9 months could led to neuroin ammatory and cognitive decline in mice [5]. However, PM 2.5 exposure induced neuroin ammatory reactions in hippocampus and cortex could be found only after 12-month exposure, which occurred after cognitive impairment, implying that neuroin ammtion may be the results but did not trigger the neuronal dysfunction [5].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we have found that chronic PM 2.5 exposure for 9 months could led to neuroin ammatory and cognitive decline in mice [5]. However, PM 2.5 exposure induced neuroin ammatory reactions in hippocampus and cortex could be found only after 12-month exposure, which occurred after cognitive impairment, implying that neuroin ammtion may be the results but did not trigger the neuronal dysfunction [5]. The underlying molecular mechanism of early events in brain induced by PM 2.5 exposure remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…In previous study, the average PM 2.5 concentration in the exposure chamber was calculated as 40.79 µg/m 3 . The main inorganic component of PM 2.5 is sulfur, while benzo(b) uoranthene has the highest proportion in PAHs [5]. Given that learning and memory de cits are the main features of cognitive dysfunction, morris water maze (MWM) test was applied to assess whether PM 2.5 exposure would impair spatial learning and memory.…”

Section: Pm 25 Exposure Attenuated Spatial Learning and Memory Abilimentioning

confidence: 99%

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S-adenosylmethionine Decarboxylase 1 Participates in PM2.5 Exposure Induced Neuronal Apoptosis via Mitochondria-Mediated Pathway

Zhu

Shou

et al. 2020

Preprint

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Background: Fine particle (Particulate matter 2.5, PM2.5), as the primary ambient pollutant, is considered harmful to some neurodegenerative diseases, while the specific biochemical mechanism underlying is still unrevealed. Neuronal apoptosis is believed the crucial event in neurodegenerative pathogenesis, but evidence supporting neuronal apoptosis as PM2.5 induced neuronal injury is insufficient. S-adenosylmethionine decarboxylase 1 (AMD1) and its related spermidine synthesis have been shown to participate in cellular apoptosis, but its role in PM2.5 exposure induced neuronal apoptosis was rarely reported. To better understand contribution of AMD1 activity and spermidine in PM2.5 exposure induced neuronal apoptosis, may provide novel therapeutic and preventive targets for air pollution associated neurodegenerative diseases.Methods: In the current work, sixteen C57BL/6 male mice were randomly divided into ambient PM2.5 chamber or filtered air chamber, and the mouse model of whole-body ambient PM2.5 chronic exposure was established. Behavioral and cognitive ability, together with corresponding biomedical index were recorded and tested to evaluated neurotoxicity by PM2.5 exposure in mice. In parallel, PC12 cells and primary hippocampal neurons were applied for PM2.5 treatment to explore the possible cellular and molecular mechanism which may be critically involved in the process. AMD1 activity and cellular spermidine content were modulated by pharmacological approach to examine their participation in PM2.5 triggered neuronal apoptosis, followed by better examination of typical index for mitochondrial membrane potential and mitochondrial-mediated apoptosis pathway signaling.Results: Chronic ambient PM2.5 exposure attenuated spatial learning and memory ability, and triggered neuronal apoptosis together with increased expression of apoptosis-related Bax/Bcl-2 and cleaved caspase-3. PM2.5 exposure impaired AMD1 expression and spermidine synthesis. AMD1 inhibition could mimick PM2.5 exposure induced neuronal apoptosis. Spermidine supplementation rescued against neurotoxicity and inhibited PM2.5 induced apoptosis, in which mitochondrial pathway signaling.Conclusions: Chronic real-time exposure to ambient PM2.5 led to the reduced the ability of spatial learning and memory in mice. Neuronal apoptosis was the key event in the process of neurodegenerative development induced by PM2.5 exposure. AMD1 and spermidine participated in neuronal apoptosis induced by PM2.5 exposure, which was at least partially dependent on mitochondria mediated pathway.

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Section: Introductionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Pm 25 Exposure Attenuated Spatial Learning and Memory Abilimentioning

confidence: 99%

See 2 more Smart Citations

S-adenosylmethionine Decarboxylase 1 Participates in PM2.5 Exposure Induced Neuronal Apoptosis via Mitochondria-Mediated Pathway

Zhu

Shou

et al. 2020

Preprint

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“…The potential pathophysiological mechanisms include inflammatory dysfunction, oxidative stress, abnormal activation of the hemostatic system, and disturbance of the autonomic nervous system [44][45][46]. Inflammation plays an important role in the development of chronic diseases [47]. Strong evidence of the association of particulate exposure with heart rate variability and systemic inflammation has been published [48].…”

Section: Discussionmentioning

confidence: 99%

Shenlian Extract in the Treatment of Ultrafine Particulate Matter- Aggravated Myocardial Ischemic Injury: Integrating Network Pharmacology and in vivo Pharmacological Evaluation

Yang

et al. 2020

Preprint

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Background: Air pollution is a growing public health burden associated with several negative health effects, especially cardiovascular disease. Shenlian extract (SL), a traditional Chinese medicine, has the effects of clearing heat-toxin and promoting blood circulation for removing blood stasis, and it has long been used to treat cardiovascular diseases and atherosclerosis. This study explored the underlying action mechanism of SL against ultrafine particle-induced myocardial ischemic injury (UFP-MI) through network pharmacology prediction and experimental verification. Methods: Male Sprague-Dawley rats with UFP-MI were pre-treated with SL intragastrically for 7 days, all the animals were randomly divided into five groups: Sham, Model (UFP+MI), SLL( 31.08mg/ kg×d) + UFP+ MI, SLM (62.16 mg/ kg×d) + UFP+MI, and SLH (124.32 mg/ kg×d) + UFP+ MI. SL or saline was administrated 7 days before UFP instillation (100 μg/kg), followed by 24 h of ischemia. Inflammatory cytokine detection and histopathological analysis were performed to assess the protective effects of SL. For the mechanism study, differentially expressed genes were identified in UFP-MI rats treated with SL through transcriptomic analysis. Subsequently, in combination with network pharmacology, potential pathways involved in the effects of SL treatment were identified using the Internet-based Computation Platform (www.tcmip.cn) and Cytoscape 3.6.0. Further validation experiments were performed to reveal the mechanism of the therapeutic effects of SL on UFP-MI.Results: In pharmacodynamics experiments, SL significantly suppressed inflammatory cell infiltration into myocardial tissue and exhibited significant anti -inflammatory activity. Transcriptomic analysis revealed that the differentially expressed genes after SL treatment had significant anti-inflammatory, immunomodulatory, and anti-viral activities. Network pharmacology analysis illustrated that the targets of SL participate in the inflammatory response, apoptotic process, innate immune response, platelet activation, and other processes. By combining transcriptomic and network pharmacology data, we found that SL may exert anti-inflammatory effects by acting on the NOD-like signaling pathway to regulate immune response activation and inhibit systemic inflammation. Verification experiments revealed that SL suppressed NLRP3 inflammasome active and inflammasomes are cytosolic protein complexes that stimulate the activation of Caspase-1, which in turn induces the secretion of the inflammatory cytokines Interleukin-1 (IL-1), Interleukin-18(IL-18) and Interleukin-33(IL-33) Conclusion: UFP can induce the activation of NLRP3 inflammasome, leading to the release of downstream the inflammatory cytokines, aggravate the pathological conditions of inflammatory infiltration, and further aggravate the myocardial ischemic injury. Experimental verification indicated that SL can directly inhibit the activation of NLRP3 inflammasomes in the NOD-like signaling pathway and reduce cytokines release. In conclusion, our results confirmed that SL may prevent UFP-MI by acting on the NOD-like signaling pathway.

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The World Trade Center Health Program: Twenty years of health effects research

Daniels

Kubale

Reissman

et al. 2021

American J Industrial Med

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It has been 20 years since the devastating terrorist attacks on September 11, 2001.Thousands were injured or killed during the attacks and many more are at risk of adverse health stemming from physical, psychological, and emotional stressors born out of the attacks. Private, federal, state, and local resources were gathered soon after the attacks to address impacts to the community, including the health and wellbeing of both responders and survivors. Many of these efforts are now largely consolidated under the federally mandated World Trade Center (WTC) Health Program. This program provides medical monitoring and treatment of qualifying conditions among the 9/11-exposed population and supports related physical and mental health research. In this commentary, we describe the WTC Health Program, with emphasis on the health-effects research it has funded since inception in 2011.We describe sentinel research publications, and how science has impacted the program. We provide examples relating studies in this special issue to important roles in the WTC Health Program research agenda. Finally, we provide a perspective on future research needs. | INTRODUCTIONAs we approach the 20th anniversary of the 9/11 terrorist attacks, we are once again reminded of the thousands who lost their lives or were injured that day. We also grieve for many more who now suffer from adverse health effects stemming from the physical, psychological, and emotional stressors born out of the attacks. The health of nearly a half million people is potentially at risk from exposures attributable to 9/11. 1 In the aftermath of the attacks, private, federal, state, and local resources supported several postdisaster activities, including recovery actions, the World Trade Center (WTC) Health Registry, and caring for the affected population in several surrounding health-care facilities. Health-care activities were later consolidated with the passing of the James Zadroga 9/11 Health and Compensation Act of 2010 (The Act), establishing the WTC Health Program 1 . The WTC Health Program is a limited health benefits program for qualifying health conditions related to the 9/11 attacks and aftermath. It provides medical monitoring and treatment of eligible responders, initial health evaluations for eligible survivors, and medical monitoring treatment for survivors who have health conditions certified by the Program. The Program resides under the U.S.

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Ambient PM2.5 chronic exposure leads to cognitive decline in mice: From pulmonary to neuronal inflammation

Cited by 43 publications

References 39 publications

S-adenosylmethionine Decarboxylase 1 Participates in PM2.5 Exposure Induced Neuronal Apoptosis via Mitochondria-Mediated Pathway

S-adenosylmethionine Decarboxylase 1 Participates in PM2.5 Exposure Induced Neuronal Apoptosis via Mitochondria-Mediated Pathway

Shenlian Extract in the Treatment of Ultrafine Particulate Matter- Aggravated Myocardial Ischemic Injury: Integrating Network Pharmacology and in vivo Pharmacological Evaluation

The World Trade Center Health Program: Twenty years of health effects research

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