Modulation of fear behavior and neuroimmune alterations in house dust mite exposed A/J mice, a model of severe asthma

Lewkowich, Ian P.; Ahlbrand, Rebecca; Johnson, E. I.; McAlees, Jaclyn W.; Nawreen, Nawshaba; Raman, Rajesh; Lingel, Imke; Hargis, Julie; Hoover, Cathy S.; Sah, Renu

doi:10.1016/j.bbi.2020.04.084

Cited by 16 publications

(6 citation statements)

References 66 publications

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“…Adolescents with asthma also had a higher risk of developing major depression compared to those without asthma (Chen et al 2014). Similar results have been found in rodent models of asthma, where mice exposed to allergens later exhibited increased anxiety-like and depression-like behaviors (Caulfield et al 2017, Lewkowich et al 2020. One possibility is that the combination of childhood asthma and air pollution contributes to neuroinflammation that effects brain structures that lead to the development of anxiety and/or depression (Caulfield 2021).…”

Section: Introductionsupporting

confidence: 56%

Effects of air pollution on emergency room visits for mental disorders: risks and effect modification by comorbid physical disorders and personal characteristics

Yoo,

Roberts,

Chen

2024

Environ. Res.: Health

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Background: Emerging evidence suggests that exposure to ambient air pol- lution negatively impacts mental health. However, little is known about potential moderators of such effects, including pre-existing physical disor- ders and personal characteristics. This study investigated if the effects of daily changes in levels of air pollutants among individuals with mental dis- orders (MDs) vary depending on comorbid physical disorders, age, sex, or race/ethnicity.Methods: We used a time-stratified case-crossover design that compared the levels of PM2.5 and NO2 on days leading up to MD-related emergency room (ER) visits to levels on control days. The sample consisted of individuals with MDs for their primary diagnosis, including both patients with second diagnosis and those without. We conducted a stratified analysis to examine the potential effect modification by individuals’ demographic characteristics (sex, age, and race/ethnicity) or a diagnosis of a physical disorder (cardio- vascular disease, diabetes mellitus, and respiratory disease). Results: We found that both PM2.5 and NO2 were significantly associated with ER visits for MDs. Per 10 μg m−3 increase in daily PM2.5 and per 10 ppb increase in NO2 concentration were associated with 1.07% (95% CI: 0.81%, 1.34%) and 0.56% (95% CI: 0.42%, 0.69%) increase in ER visits for MDs, respectively. We also found significantly greater susceptibility among younger persons (below 18 years old), Black, and individuals with respiratory disease. Conclusions: Exposures to both PM2.5 and NO2 were significantly associated with ER visits for MDs, and these adverse effects were more pronounced among youth, Black and individuals with respiratory disease as a comorbid physical disorder.

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Section: Introductionsupporting

confidence: 56%

Effects of air pollution on emergency room visits for mental disorders: risks and effect modification by comorbid physical disorders and personal characteristics

Yoo,

Roberts,

Chen

2024

Environ. Res.: Health

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“…Asthma is a complex heterogeneous disorder with multiple etiologies and molecular phenotypes (eosinophilic, neutrophilic, paucigranulocytic, based on the nature of airway inflammation) 9–11 . A growing body of research suggests that the adverse effects of asthma on the brain 12,13 are mediated by neuroinflammatory processes, potentially via the interleukin‐17 pathway, 14 though hypoxia and changes to the neurovasculature 15 are additional possible mechanisms. Allergen exposure in mouse models of asthma, for example, activates microglial cells and evokes pro‐inflammatory cytokine expression, as well as deleterious structural brain changes, in regions relevant to dementia and Alzheimer's disease (AD) 16,17 .…”

Section: Introductionmentioning

confidence: 99%

Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline

Nair

Hulle

Bendlin

et al. 2022

A&D Transl Res & Clin Interv

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Introduction Evidence from epidemiology, neuroimaging, and animal models indicates that asthma adversely affects the brain, but the nature and extent of neuropathophysiological impact remain unclear. Methods We tested the hypothesis that asthma is a risk factor for dementia by comparing cognitive performance and cerebrospinal fluid biomarkers of glial activation/neuroinflammation, neurodegeneration, and Alzheimer's disease (AD) pathology in 60 participants with asthma to 315 non‐asthma age‐matched control participants (45–93 years), in a sample enriched for AD risk. Results Participants with severe asthma had higher neurogranin concentrations compared to controls and those with mild asthma. Positive relationships between cardiovascular risk and concentrations of neurogranin and α‐synuclein were amplified in severe asthma. Severe asthma also amplified the deleterious associations that apolipoprotein E ε4 carrier status, cardiovascular risk, and phosphorylated tau 181 /amyloid beta 42 have with rate of cognitive decline. Discussion Our data suggest that severe asthma is associated with synaptic degeneration and may compound risk for dementia posed by cardiovascular disease and genetic predisposition. Highlights Those with severe asthma showed evidence of higher dementia risk than controls evidenced by: higher levels of the synaptic degeneration biomarker neurogranin regardless of cognitive status, cardiovascular or genetic risk, and controlling for demographics. steeper increase in levels of synaptic degeneration biomarkers neurogranin and α‐synuclein with increasing cardiovascular risk. accelerated cognitive decline with higher cardiovascular risk, genetic predisposition, or pathological tau.

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“…It has been widely used in an established mouse asthma model that closely resembles human allergic asthma. Previously, after intratracheal HDM sensitization in A/J mice, reduced motor activity that persisted for only one day was observed in the elevated zero maze [ 29 ] that was used to test anxiety-like behaviors. In these prior studies, HDM sensitization was performed once a week for 3 weeks, totaling three times, and other behavioral testing was conducted after fear conditioning by CO 2 inhalation: therefore, the experimental paradigm and duration of HDM sensitization are both very different from the current study.…”

Section: Discussionmentioning

confidence: 99%

Chronic allergic lung inflammation negatively influences neurobehavioral outcomes in mice

Kanaya

Yang

Emala

et al. 2022

J Neuroinflammation

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Background Asthma is a major public health problem worldwide. Emerging data from epidemiological studies show that allergies and allergic diseases may be linked to anxiety, depression and cognitive decline. However, little is known about the effect of asthma, an allergic lung inflammation, on cognitive decline/behavioral changes. Therefore, we investigated the hypothesis that allergic lung inflammation causes inflammation in the brain and leads to neurobehavioral changes in mice. Methods Wild-type C57BL/6J female mice were sensitized with nasal house dust mite (HDM) antigen or control PBS for 6 weeks to induce chronic allergic lung inflammation. A series of neurocognitive tests for anxiety and/or depression were performed before and after the intranasal HDM administration. After the behavior tests, tissues were harvested to measure inflammation in the lungs and the brains. Results HDM-treated mice exhibited significantly increased immobility times during tail suspension tests and significantly decreased sucrose preference compared with PBS controls, suggesting a more depressed and anhedonia phenotype. Spatial memory impairment was also observed in HDM-treated mice when assessed by the Y-maze novel arm tests. Development of lung inflammation after 6 weeks of HDM administration was confirmed by histology, bronchoalveolar lavage (BAL) cell count and lung cytokine measurements. Serum pro-inflammatory cytokines and Th2-related cytokines levels were elevated in HDM-sensitized mice. In the brain, the chemokine fractalkine was increased in the HDM group. The c-Fos protein, a marker for neuronal activity, Glial Fibrillary Acidic Protein (GFAP) and chymase, a serine protease from mast cells, were increased in the brains from mice in HDM group. Chymase expression in the brain was negatively correlated with the results of sucrose preference rate in individual mice. Conclusions 6 weeks of intranasal HDM administration in mice to mimic the chronic status of lung inflammation in asthma, caused significant inflammatory histological changes in the lungs, and several behavioral changes consistent with depression and altered spatial memory. Chymase and c-Fos proteins were increased in the brain from HDM-treated mice, suggesting links between lung inflammation and brain mast cell activation, which could be responsible for depression-like behavior.

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Modulation of fear behavior and neuroimmune alterations in house dust mite exposed A/J mice, a model of severe asthma

Cited by 16 publications

References 66 publications

Effects of air pollution on emergency room visits for mental disorders: risks and effect modification by comorbid physical disorders and personal characteristics

Effects of air pollution on emergency room visits for mental disorders: risks and effect modification by comorbid physical disorders and personal characteristics

Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline

Chronic allergic lung inflammation negatively influences neurobehavioral outcomes in mice

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