Exposure to World Trade Center Dust Exacerbates Cognitive Impairment and Evokes a Central and Peripheral Pro-Inflammatory Transcriptional Profile in an Animal Model of Alzheimer’s Disease

Abstract

Background: The terrorist attacks on September 11, 2001, on the World Trade Center (WTC) led to intense fires and a massive dense cloud of toxic gases and suspended pulverized debris. In the subsequent years, following the attack and cleanup efforts, a cluster of chronic health conditions emerged among First Responders (FR) who were at Ground Zero for prolonged periods and were repeatedly exposed to high levels of WTC particulate matter (WTCPM). Among those are neurological complications which may increase the risk for the development of Alzheimer’s disease (AD) later in life. Objective: We hypothesize that WTCPM dust exposure affects the immune cross-talking between the periphery and central nervous systems that may induce brain permeability ultimately promoting AD-type phenotype. Methods: 5XFAD and wild-type mice were intranasally administered with WTCPM dust collected at Ground Zero within 72 h after the attacks. Y-maze assay and novel object recognition behavioral tests were performed for working memory deficits and learning and recognition memory, respectively. Transcriptomic analysis in the blood and hippocampus was performed and confirmed by RT qPCR. Results: Mice exposed to WTCPM dust exhibited a significant impairment in spatial and recognition short and long-term memory. Furthermore, the transcriptomic analysis in the hippocampal formation and blood revealed significant changes in genes related to immune-inflammatory responses, and blood-brain barrier disruption. Conclusion: These studies suggest a putative peripheral-brain immune inflammatory cross-talking that may potentiate cognitive decline, identifying for the first time key steps which may be therapeutically targetable in future studies in WTC FR.

World Trade Center Exposure, DNA Methylation Changes, and Cancer: A Review of Current Evidence

“…PRKACA, which was hypermethylated among WTC-associated cancers, is vital for the attenuation of innate immune response, avoiding host damage during later stages of immune reaction [67]. These results are consistent with previous studies that have demonstrated that WTC exposure is associated with immune system dysregulation [12,68,69]. Gong et al previously showed that WTC prostate tumors are enriched for proinflammatory Th17 cells [12].…”

“…Gong et al previously showed that WTC prostate tumors are enriched for proinflammatory Th17 cells [12]. In rats experimentally exposed to WTC dust, gene expression changes in immune-inflammatory response have been observed [12,68,69].…”

Pasteurized Akkermansia muciniphila improves irritable bowel syndrome-like symptoms and related behavioral disorders in mice

“…Cognitive performance was then evaluated using the Y-maze test to assess working memory 26 and the NOR/NLR behavioral test for learning and recognition memory. 27 During the Y-maze assay, the percentage of alternation was significantly lower in the Citro/Veh mouse group than in the non-infected NI/Veh mouse group ( Figure 5d ). However, this parameter did not return to a normal spontaneous alternation in infected mice even after a treatment with pasteurized A. muciniphila ( Figure 5d ).…”

Ru360 Alleviates Postoperative Cognitive Dysfunction in Aged Mice by Inhibiting MCU-Mediated Mitochondrial Dysfunction

“…Recognition index: [Time at the novel object / (Time at the novel object + Time at the familiar object)] x 100 (%). 16 Mice with poor cognitive ability showed no difference in the exploration of new and old objects. Mice with normal cognitive ability showed longer exploration of new objects than those with old objects.…”