Interaction of opioid with insulin/IGFs signaling in Alzheimer's disease

Salarinasab, Sadegh; Salimi, Leila; Alidadiani, Neda; Shokrollahi, Elhameh; Arzhang, Pishva; Karbasforush, Saedeh; Marofi, Faroogh; Nasirzadeh, Mahdieh; Rahbarghazi‬, Reza; Nourazarian, Alireza; Nikanfar, Masoud

doi:10.1007/s12031-020-01478-y

Cited by 9 publications

(6 citation statements)

References 143 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found evidence of co-expression in genes involved in neurogenesis pathways, cell differentiation, and neuronal development for both 5mC and 5hmC. Previous studies have shown that opioids decrease neurogenesis by inhibiting cell division, mainly by blocking the S phase 32 . We detected one differential 5hmC annotated gene in two 5hmC modules, CCT2 gene in navajowhite3 and rosybrown1, while no annotated genes were observed for 5mC.…”

Section: Discussionsupporting

confidence: 50%

See 1 more Smart Citation

Profiling Neuronal Methylome and Hydroxymethylome of Opioid Use Disorder in the Human Orbitofrontal Cortex

Rompala

Nagamatsu

Martínez‐Magaña

et al. 2022

Preprint

View full text Add to dashboard Cite

Opioid use disorder (OUD) is influenced by genetic and environmental factors. While recent research suggests that there are epigenetic disturbances in OUD, these studies were limited to DNA methylation (5mC). DNA hydroxymethylation (5hmC) has been understudied in psychiatric disorders and addiction, despite being highly enriched in the brain where it regulates critical functions, including neural plasticity. Here, we conducted a multi-omic profiling of the orbitofrontal cortex (OFC) of OUD, integrating neuronal-specific 5mC and 5hmC as well as within-subject correlations with gene expression profiles from human postmortem samples (OUD=12; controls=26). Further, co-methylation modules and GWAS enrichment were analyzed for 5mC and 5hmC. Evaluation of single locus methylomic alterations identified 397 and 1740 differentially 5mC and 5hmC CpGs, respectively. Enrichment for neuronal function was observed for 5hmC, while no significant pathways were observed for 5mC. 5mC and 5hmC co-methylation analysis identified modules associated with OUD enriched for Pre-NOTCH Transcription and Translation, and WNT signaling. Transcriptomic analysis identified HBB as significantly associated with OUD. Finally, drug interaction analysis showed seven differential 5hmC genes and one differential 5mC gene interacting with opioid use. Our multi-omic findings suggest an important role of 5hmC and reveal novel loci epigenetically dysregulated in OFC neurons of individuals with OUD.

show abstract

Section: Discussionsupporting

confidence: 50%

“…Previous studies have shown that opioids decrease neurogenesis by inhibiting cell division, mainly by blocking the S phase 32 . We detected one differential 5hmC annotated gene in two 5hmC modules, CCT2 gene in navajowhite3 and rosybrown1, while no annotated genes were observed for 5mC.…”

Section: Discussionmentioning

confidence: 98%

Profiling Neuronal Methylome and Hydroxymethylome of Opioid Use Disorder in the Human Orbitofrontal Cortex

Rompala

Nagamatsu

Martínez‐Magaña

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Chronic exposure to opioid drugs, such as morphine, is known to inhibit the insulin signaling pathway, leading to alterations in glucose homeostasis, and an increased risk of developing insulin resistance and associated comorbidities 33 , 34 . The PPI analysis for the modules showed evidence of co-expression in genes involved in neurogenesis pathways, which corroborates previous studies showing that opioids decrease neurogenesis by inhibiting cell division, mainly through blocking the S phase 35 . It also revealed an interaction with one differential 5hmC annotated gene, CCT2 , present in the navajowhite3 and rosybrown1 modules, while no annotated genes were observed for 5mC.…”

Section: Discussionsupporting

confidence: 88%

Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex

Rompala,

Nagamatsu,

Martínez-Magaña

et al. 2023

Nat Commun

View full text Add to dashboard Cite

Opioid use disorder (OUD) is influenced by genetic and environmental factors. While recent research suggests epigenetic disturbances in OUD, this is mostly limited to DNA methylation (5mC). DNA hydroxymethylation (5hmC) has been widely understudied. We conducted a multi-omics profiling of OUD in a male cohort, integrating neuronal-specific 5mC and 5hmC as well as gene expression profiles from human postmortem orbitofrontal cortex (OUD = 12; non-OUD = 26). Single locus methylomic analysis and co-methylation analysis showed a higher number of OUD-associated genes and gene networks for 5hmC compared to 5mC; these were enriched for GPCR, Wnt, neurogenesis, and opioid signaling. 5hmC marks also showed a higher correlation with gene expression patterns and enriched for GWAS of psychiatric traits. Drug interaction analysis revealed interactions with opioid-related drugs, some used as OUD treatments. Our multi-omics findings suggest an important role of 5hmC and reveal loci epigenetically dysregulated in OFC neurons of individuals with OUD.

show abstract

“…These processes are regulated by insulin directly [67]. Under normal conditions, insulin binds to the insulin receptor on the plasma membrane of adipocytes [68] and initiates downstream metabolic signaling by recruiting phosphotyrosine-binding scaffold proteins, which in turn activate phosphoinositide-3-kinase (PI3K) [69][70][71][72]. The critical physiological functions of this signaling pathway in white adipose tissue include the suppression of lipolysis and stimulation of glucose uptake and lipogenesis [67].…”

Section: The Effects Of Mir-320 On Glucose and Lipid Metabolism In Whmentioning

confidence: 99%

The role of miR-320 in glucose and lipid metabolism disorder-associated diseases

Zhang

Yin

et al. 2021

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Interaction of opioid with insulin/IGFs signaling in Alzheimer's disease

Cited by 9 publications

References 143 publications

Profiling Neuronal Methylome and Hydroxymethylome of Opioid Use Disorder in the Human Orbitofrontal Cortex

Profiling Neuronal Methylome and Hydroxymethylome of Opioid Use Disorder in the Human Orbitofrontal Cortex

Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex

The role of miR-320 in glucose and lipid metabolism disorder-associated diseases

Contact Info

Product

Resources

About