Methylation of the<i>AIM2</i>gene: An epigenetic mediator of PTSD‐related inflammation and neuropathology plasma biomarkers

Hawn, Sage E.; Neale, Zoë; Wolf, Erika J.; Zhao, Xiang; Pierce, Meghan; Fein‐Schaffer, Dana; Milberg, William; McGlinchey, Regina E.; Logue, Mark W.

doi:10.1002/da.23247

Cited by 7 publications

(6 citation statements)

References 36 publications

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“…Several studies examined epigenetic mechanisms, that is, environmentally sensitive structural changes to DNA conformation that can influence gene expression (Aristizabal et al, 2019 ). Hawn et al ( 2022 ) examined whether methylation in AIM2 , a gene previously linked to inflammation, was associated with PTSD symptom severity and mediated the relationship between PTSD symptomology and markers of inflammation and neuropathology in a cohort of military veterans. The analyses indicated both time- and outcome-dependent effects of methylation.…”

Section: Resultsmentioning

confidence: 99%

“…Two studies directly investigated inflammatory mechanisms. Though the functional effects of the IL-10 SNP rs1800872 investigated by Chen et al ( 2022 ) is unknown, Hawn et al ( 2022 ) found evidence that a more proinflammatory environment may contribute to PTSD with higher circulating levels of proinflammatory cytokines and lower levels of an anti-inflammatory cytokine predicting worse PTSD symptom severity at baseline and 2 years, respectively. Inflammation is also reciprocally related to the activity of the hypothalamus-pituitary–adrenal axis, which is activated upon threat perception, coordinates the stress response, and may affect cognition and mood (Leistner and Menke, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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Advances in the molecular neurobiology of posttraumatic stress disorder from global contexts: A systematic review of longitudinal studies

Womersley,

du Plessis,

Greene

et al. 2023

Camb. prisms Glob. ment. health

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Trauma exposure is prevalent globally and is a defining event for the development of posttraumatic stress disorder (PTSD), characterised by intrusive thoughts, avoidance behaviours, hypervigilance and negative alterations in cognition and mood. Exposure to trauma elicits a range of physiological responses which can interact with environmental factors to confer relative risk or resilience for PTSD. This systematic review summarises the findings of longitudinal studies examining biological correlates predictive of PTSD symptomology. Databases (Pubmed, Scopus and Web of Science) were systematically searched using relevant keywords for studies published between 1 January 2021 and 31 December 2022. English language studies were included if they were original research manuscripts or meta-analyses of cohort investigations that assessed longitudinal relationships between one or more molecular-level measures and either PTSD status or symptoms. Eighteen of the 1,042 records identified were included. Studies primarily included military veterans/personnel, individuals admitted to hospitals after acute traumatic injury, and women exposed to interpersonal violence or rape. Genomic, inflammation and endocrine measures were the most commonly assessed molecular markers and highlighted processes related to inflammation, stress responding, and learning and memory. Quality assessments were done using the Systematic Appraisal of Quality in Observational Research, and the majority of studies were rated as being of high quality, with the remainder of moderate quality. Studies were predominantly conducted in upper-income countries. Those performed in low- and middle-income countries were not broadly representative in terms of demographic, trauma type and geographic profiles, with three out of the four studies conducted assessing only female participants, rape exposure and South Africa, respectively. They also did not generate multimodal data or use machine learning or multilevel modelling, potentially reflecting greater resource limitations in LMICs. Research examining molecular contributions to PTSD does not adequately reflect the global burden of the disorder.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Advances in the molecular neurobiology of posttraumatic stress disorder from global contexts: A systematic review of longitudinal studies

Womersley,

du Plessis,

Greene

et al. 2023

Camb. prisms Glob. ment. health

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“…The stop-gain variant in the AIM2 gene, whose definite site is rs2276405 ( Figure 1B ), is significantly enriched in psoriasis ( 43 ). Methylation of the AIM2 gene at the site cg10636246 drives the relationship between trauma exposure, posttraumatic stress disorder (PTSD), the level of C-reactive protein (CRP) and other inflammatory mediators, such as IL-6, IL-10, and TNF-α, in the body ( 44 , 45 ). MicroRNA (miRNA), a non-coding RNA (ncRNA) of approximately 22 nucleotides in length, binds to messenger RNA (mRNA) targets of inflammasome genes for post-transcriptional regulation of inflammasome expression ( 46 ).…”

Section: Genetic and Epigenetic Control Of The Aim2 Inflammasomementioning

confidence: 99%

AIM2 and Psoriasis

Zhang

Cheng

et al. 2023

Front. Immunol.

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Psoriasis is a chronic inflammatory skin disease occurring worldwide, with multiple systemic complications, which seriously affect the quality of life and physical and mental health of patients. The pathogenesis of psoriasis is related to the environment, genetics, epigenetics, and dysregulation of immune cells such as T cells, dendritic cells (DCs), and nonimmune cells such as keratinocytes. Absent in melanoma 2 (AIM2), a susceptibility gene locus for psoriasis, has been strongly linked to the genetic and epigenetic aspects of psoriasis and increased in expression in psoriatic keratinocytes. AIM2 was found to be activated in an inflammasome-dependent way to release IL-1β and IL-18 to mediate inflammation, and to participate in immune regulation in psoriasis, or in an inflammasome-independent way by regulating the function of regulatory T(Treg) cells or programming cell death in keratinocytes as well as controlling the proliferative state of different cells. AIM2 may also play a role in the recurrence of psoriasis by trained immunity. In this review, we will elaborate on the characteristics of AIM2 and how AIM2 mediates the development of psoriasis.

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“…The same study also indicated that NLRP1-mediated caspase-1 activation produces pyroptosis [ 123 , 124 ]. Moreover, several investigations have demonstrated that substantial AIM2 inflammasome activation was detected in neurodevelopment [ 67 , 125 ], and abnormalities in AIM2 result in anxiety-related behaviors in mice [ 53 , 126 ]. The AIM2 inflammasome also contributes to CNS homeostasis by regulating gasdermin-D activity [ 67 ].…”

Section: Potential Research Directions For Pocdmentioning

confidence: 99%

Bridging the Gap: Investigating the Link between Inflammasomes and Postoperative Cognitive Dysfunction

Zhang¹,

Liu²,

Sun³

et al. 2023

Aging and disease

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Postoperative cognitive dysfunction (POCD) is a cluster of cognitive problems that may arise after surgery. POCD symptoms include memory loss, focus inattention, and communication difficulties. Inflammasomes, intracellular multiprotein complexes that control inflammation, may have a significant role in the development of POCD. It has been postulated that the NLRP3 inflammasome promotes cognitive impairment by triggering the inflammatory response in the brain. Nevertheless, there are many gaps in the current literature to understand the underlying pathophysiological mechanisms and develop future therapy. This review article underlines the limits of our current knowledge about the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome and POCD. We first discuss inflammasomes and their types, structures, and functions, then summarize recent evidence of the NLRP3 inflammasome's involvement in POCD. Next, we propose a hypothesis that suggests the involvement of inflammasomes in multiple organs, including local surgical sites, blood circulation, and other peripheral organs, leading to systemic inflammation and subsequent neuronal dysfunction in the brain, resulting in POCD. Research directions are then discussed, including analyses of inflammasomes in more clinical POCD animal models and clinical trials, studies of inflammasome types that are involved in POCD, and investigations into whether inflammasomes occur at the surgical site, in circulating blood, and in peripheral organs. Finally, we discuss the potential benefits of using new technologies and approaches to study inflammasomes in POCD. A thorough investigation of inflammasomes in POCD might substantially affect clinical practice.

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Methylation of theAIM2gene: An epigenetic mediator of PTSD‐related inflammation and neuropathology plasma biomarkers

Cited by 7 publications

References 36 publications

Advances in the molecular neurobiology of posttraumatic stress disorder from global contexts: A systematic review of longitudinal studies

Advances in the molecular neurobiology of posttraumatic stress disorder from global contexts: A systematic review of longitudinal studies

AIM2 and Psoriasis

Bridging the Gap: Investigating the Link between Inflammasomes and Postoperative Cognitive Dysfunction

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