Epigenetics of neuroinflammation: Immune response, inflammatory response and cholinergic synaptic involvement evidenced by genome-wide DNA methylation analysis of delirious inpatients

Saito, Taku; Toda, Hiroyuki; Duncan, Gabrielle N.; Jellison, Sydney S.; Yu, Tong; Klisares, Mason J.; Daniel, Sophia; Andreasen, Allison; Leyden, Lydia R; Hellman, Mandy M.; Shinozaki, Eri; Lee, Sangil; Yoshino, Aihide; Cho, Hyunkeun R.; Shinozaki, Gen

doi:10.1016/j.jpsychires.2020.06.005

Cited by 22 publications

(28 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In elderly subjects, aseptic inflammatory processes may develop at the fracture site soon after the accident [33]. In addition, this inflammatory response in delirious patients was also evidenced at the epigenetic level, which was previously described by the DNA methylation study of Saito et al [34]. Overall, our findings in hip fracture patients support the theory that immune-inflammatory processes [35-37] play a role in the pathophysiology of delirium.…”

Section: Discussionsupporting

confidence: 84%

Immune, Blood Cell, and Blood Gas Biomarkers of Delirium in Elderly Individuals with Hip Fracture Surgery

Thisayakorn

Tangwongchai

Tantavisut

et al. 2021

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

Background: Postoperative delirium in elderly people with hip fracture is associated with various adverse clinical outcomes. Nevertheless, the pathophysiological processes underpinning delirium have remained elusive. Objectives: The aim of this study was to explore the associations between delirium and its features and immune-inflammatory and blood gas biomarkers. Methods: In this prospective study, we examined 65 patients who underwent a hip fracture surgery and assessed the Confusion Assessment Method for the Intensive Care Unit, Richmond Agitation-Sedation Scale (RASS), and Delirium Rating Scale Revised-98 (DRS-R-98) before and during 4 days after the surgery. Complete blood count and venous blood gas markers were obtained at the same time points. Results: Delirium was observed in 19 patients and was accompanied by significantly increased pO2, number of white blood cells, neutrophil percentage, and neutrophil/lymphocyte ratio, and lower mean platelet volume (MPV) after adjusting for age, central nervous system (CNS) disease, blood loss during surgery, sleep disorders, and body mass index. The severity of delirium was associated with lowered number of platelets and MPV. Psychomotor disorders were associated with lower bicarbonate levels. The requirement of physical restraint of the patients was predicted by increased percentages of neutrophils and lymphocytes. Prior CNS disease was together with these biomarkers a significant predictor of delirium and severity of delirium. Conclusion: Delirium and psychomotor disorders following hip fracture and surgery may be caused by immune-inflammatory and oxidative stress pathways probably attributable to an aseptic inflammatory process.

show abstract

Section: Discussionsupporting

confidence: 84%

Immune, Blood Cell, and Blood Gas Biomarkers of Delirium in Elderly Individuals with Hip Fracture Surgery

Thisayakorn

Tangwongchai

Tantavisut

et al. 2021

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

show abstract

“…Furthermore, we must take into account that there are factors other than genetic variants that may influence the expression of relevant genes, which could lead to the development of POD and POCD. For example, there are already studies suggesting that epigenetic regulation of mainly proinflammatory [ 30 ] and also neurotransmitter genes, especially cholinergic genes [ 31 ] may be involved in the development of delirium.…”

Section: Discussionmentioning

confidence: 99%

Association between genetic variants of the cholinergic system and postoperative delirium and cognitive dysfunction in elderly patients

et al. 2021

View full text Add to dashboard Cite

Background Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are frequent and serious complications after surgery. We aim to investigate the association between genetic variants in cholinergic candidate genes according to the Kyoto encyclopedia of genes and genomes - pathway: cholinergic neurotransmission with the development of POD or POCD in elderly patients. Methods This analysis is part of the European BioCog project (www.biocog.eu), a prospective multicenter observational study with elderly surgical patients. Patients with a Mini-Mental-State-Examination score ≤ 23 points were excluded. POD was assessed up to seven days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method and a patient chart review. POCD was assessed three months after surgery with a neuropsychological test battery. Genotyping was performed on the Illumina Infinium Global Screening Array. Associations with POD and POCD were analyzed using logistic regression analysis, adjusted for age, comorbidities and duration of anesthesia (for POCD analysis additionally for education). Odds ratios (OR) refer to minor allele counts (0, 1, 2). Results 745 patients could be included in the POD analysis, and 452 in the POCD analysis. The rate of POD within this group was 20.8% (155 patients), and the rate of POCD was 10.2% (46 patients). In a candidate gene approach three genetic variants of the cholinergic genes CHRM2 and CHRM4 were associated with POD (OR [95% confidence interval], rs8191992: 0.61[0.46; 0.80]; rs8191992: 1.60[1.22; 2.09]; rs2067482: 1.64[1.10; 2.44]). No associations were found for POCD. Conclusions We found an association between genetic variants of CHRM2 and CHRM4 and POD. Further studies are needed to investigate whether disturbances in acetylcholine release and synaptic plasticity are involved in the development of POD. Trial registration: ClinicalTrials.gov: NCT02265263.

show abstract

“…Yang et al [ 32 ] showed that inhibition of NF- κ b, which is dependent on estrogen receptor α , inhibits the production of IL-6, and thus, reduces inflammation. Saito et al [ 33 ] showed that cholinergic synapses can induce an immune-inflammatory response that can cause pancreatic edema and bleeding. The FOXO1 signaling pathway plays an important role in cell metabolism, oxidative stress, cell proliferation, and apoptosis [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Elucidating the Mechanism of Action of Salvia miltiorrhiza for the Treatment of Acute Pancreatitis Based on Network Pharmacology and Molecular Docking Technology

Zhu

Zhang

Long

et al. 2021

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

Using network pharmacology and molecular docking, this study investigated the molecular mechanisms by which the active components in Salvia miltiorrhiza can alleviate acute pancreatitis. Initially, the active components of Salvia miltiorrhiza and the targets collected from the GeneCards database were screened based on the platform of systematic pharmacology analysis of traditional Chinese medicine. Subsequently, the active components were intersected with the disease targets. Also, interactions among the targets were computed using the STRING database. Biological function and pathway enrichment were analyzed using the Cluster Profiler package in the R software. Protein-protein interaction and component target pathway network were constructed using the Cytoscape software. Ultimately, the key targets and their corresponding components in the network were verified using the AutoDock Vina software. The results showed Salvia miltiorrhiza had 111 targets for acute pancreatitis. The biological process (BP) analysis showed that the active components of Salvia miltiorrhiza induced a drug response, positive regulation of transcription by RNA polymerase II promoter, signal transduction, positive regulation of cell proliferation, and negative regulation of apoptosis. Furthermore, the KEGG enrichment analysis screened 118 ( P < 0.05 ) signaling pathways, such as the pathways related to cancer, neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway, and cAMP signaling pathway, to name a few. Finally, molecular docking showed that the active components of Salvia miltiorrhiza had a good binding affinity with their corresponding target proteins. Through network pharmacology, this study predicted the potential pharmacodynamic material basis and the mechanisms by which Salvia miltiorrhiza can treat acute pancreatitis. Moreover, this study provided a scientific basis for mining the pharmacodynamic components of Salvia miltiorrhiza and expanding the scope of its clinical use.

show abstract

Epigenetics of neuroinflammation: Immune response, inflammatory response and cholinergic synaptic involvement evidenced by genome-wide DNA methylation analysis of delirious inpatients

Cited by 22 publications

References 34 publications

Immune, Blood Cell, and Blood Gas Biomarkers of Delirium in Elderly Individuals with Hip Fracture Surgery

Immune, Blood Cell, and Blood Gas Biomarkers of Delirium in Elderly Individuals with Hip Fracture Surgery

Association between genetic variants of the cholinergic system and postoperative delirium and cognitive dysfunction in elderly patients

Elucidating the Mechanism of Action of Salvia miltiorrhiza for the Treatment of Acute Pancreatitis Based on Network Pharmacology and Molecular Docking Technology

Contact Info

Product

Resources

About