Coordination of Gene Expression of Arachidonic and Docosahexaenoic Acid Cascade Enzymes during Human Brain Development and Aging

Ryan, Veronica H.; Primiani, Christopher T.; Rao, Jagadeesh S.; Ahn, Kwangmi; Rapoport, Stanley I.; Blanchard, H.

doi:10.1371/journal.pone.0100858

Cited by 25 publications

(33 citation statements)

References 81 publications

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“…Silencing of CCNA2, which controled both the G1/S and the G2/M transition phases of the cell cycle, emarkably triggered the cellular aging, while CCNA2 overexpression delayed cellular aging [38]. The expression of PTGS with a particular role in the in ammatory response was up-regulated in diseases related to brain aging [39]. PPARG, key regulator of adipocyte differentiation and glucose homeostasis, was associated with in ammation [40].…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology-based strategy to investigate pharmacological mechanisms of Ginkgo Biloba Extract for Aging

Liu

Zhang

et al. 2020

Preprint

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Background Aging represents the main risk factor for a number of debilitating diseases and contributes to increase in mortality. Previous studies have shown that ginkgo biloba extract (EGb) can prevent and treat aging-related diseases, but its pharmacological effects need to be further clarified. In this study, we proposed a network pharmacology-based method to identify the therapeutic pathways of EGb for aging.Methods The active components of EGb and targets of sample chemicals were obtained from TCMSP database. Aging-related genes were obtained by retrieving the Human Ageing Genomic Resources database and the JenAge Ageing Factor Database. Then, a network containing the interactions between the putative targets of EGb and known therapeutic targets of aging was built, which was used to investigate pharmacological mechanisms of EGb for Aging.Results 24 active components, 154 targets of active components of EGb and 308 targets of aging were obtained. Network construction and pathway enrichment were carried out after data integration. The research found that flavonoids (quercetin, luteolin, kaempferol) and beta-sitosterol might be the main active component of EGb. The top eight candidate targets, including PTGS2, PPARG, DPP4, GSK3B, CCNA2, AR, MAPK14, ESR1, were chosen as EGb’s main therapeutic targets. The results of pathway enrichment participated in various pathways associated with inhibiting oxidative stress, inhibiting inflammation, ameliorating insulin resistance and regulating cellular biological processes, etc. Molecular docking results showed that PPARG had better binding capacity with beta-sitosterol and PTGS2 had better binding capacity with kaempferol and quercetin.Conclusions The main components of EGb might act on multiple targets, such as PTGS2, PPARG, DPP4, GSK3B, etc., to regulate multiple pathways and played an anti- aging role by inhibiting oxidative stress, inhibiting inflammation, ameliorating insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Network pharmacology-based strategy to investigate pharmacological mechanisms of Ginkgo Biloba Extract for Aging

Liu

Zhang

et al. 2020

Preprint

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“…One possibility is that n-3 PUFA supplementation without concurrent dietary reduction of n-6 PUFAs may not produce therapeutically-relevant alterations in the interactive brain n-6 and n-3 PUFA pathways. 83,84 In this regard, in the past 100 years, there has been an increase in consumption of the n-6 PUFA precursor LA in the average US diet – the predictable effect of this is increasing tissue concentrations of LA, and decreasing tissue concentrations of n-3 EPA and DHA, and thus an imbalance of n-6 over n-3 PUFAs and their metabolites. 85 Simple addition of an n-3 PUFA supplement without concurrent reduction in dietary n-6 LA may not alter brain PUFA metabolism to the extent required to produce clinically meaningful benefit.…”

Section: The Way Forward: Lessons From Migrainementioning

confidence: 99%

Reconsidering Dietary Polyunsaturated Fatty Acids in Bipolar Disorder: A Translational Picture

Saunders

Ramsden

Sherazy

et al. 2016

J. Clin. Psychiatry

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Inflammation is an important mediator of pathophysiology in bipolar disorder (BD). The omega (n)-3 and omega (n)-6 polyunsaturated fatty acid (PUFA) metabolic pathways participate in several inflammatory processes, and have been linked through epidemiological and clinical studies to BD and its response to treatment. We review the proposed role of PUFA metabolism in neuroinflammation, modulation of brain PUFA metabolism by antimanic medications in rodent models, and anti-inflammatory pharmacotherapy in BD and in major depressive disorder (MDD). Though the convergence of findings between pre-clinical and post-mortem clinical data is compelling, we investigate why human trials of PUFA as treatment are mixed. We view the biomarker and treatment study findings in light of the evidence for the hypothesis that arachidonic acid (AA) hypermetabolism contributes to BD pathophysiology, and propose that a combined high n-3 plus low n-6 diet should be tested as an adjunct to current medication in future trials.

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“…To address this limitation, in the present study we analyzed age changes over the lifespan in brain mRNA levels of 39 genes whose protein products have been reported to be involved in neuroinflammation, synaptic integrity, neurotrophic effects, and related processes. As in our prior report on age expression of brain lipid metabolic markers [47] , we employed the large-scale microarray dataset called BrainCloud, which contains genome-wide expression levels in frontal cortex from non-pathological individuals, in the fetal period to postnatal 78 years of age [48] . Similarly, and consistent with the literature, we considered gene expression in two distinct postnatal age intervals, Development (0 to 21 years) and Aging (22 to 78 years) [35] , [47] , [49] , [50] , henceforth identified by capitalizations.…”

Section: Introductionmentioning

confidence: 99%

Coordinated Gene Expression of Neuroinflammatory and Cell Signaling Markers in Dorsolateral Prefrontal Cortex during Human Brain Development and Aging

et al. 2014

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BackgroundAge changes in expression of inflammatory, synaptic, and neurotrophic genes are not well characterized during human brain development and senescence. Knowing these changes may elucidate structural, metabolic, and functional brain processes over the lifespan, as well vulnerability to neurodevelopmental or neurodegenerative diseases.HypothesisExpression levels of inflammatory, synaptic, and neurotrophic genes in the human brain are coordinated over the lifespan and underlie changes in phenotypic networks or cascades.MethodsWe used a large-scale microarray dataset from human prefrontal cortex, BrainCloud, to quantify age changes over the lifespan, divided into Development (0 to 21 years, 87 brains) and Aging (22 to 78 years, 144 brains) intervals, in transcription levels of 39 genes.ResultsGene expression levels followed different trajectories over the lifespan. Many changes were intercorrelated within three similar groups or clusters of genes during both Development and Aging, despite different roles of the gene products in the two intervals. During Development, changes were related to reported neuronal loss, dendritic growth and pruning, and microglial events; TLR4, IL1R1, NFKB1, MOBP, PLA2G4A, and PTGS2 expression increased in the first years of life, while expression of synaptic genes GAP43 and DBN1 decreased, before reaching plateaus. During Aging, expression was upregulated for potentially pro-inflammatory genes such as NFKB1, TRAF6, TLR4, IL1R1, TSPO, and GFAP, but downregulated for neurotrophic and synaptic integrity genes such as BDNF, NGF, PDGFA, SYN, and DBN1.ConclusionsCoordinated changes in gene transcription cascades underlie changes in synaptic, neurotrophic, and inflammatory phenotypic networks during brain Development and Aging. Early postnatal expression changes relate to neuronal, glial, and myelin growth and synaptic pruning events, while late Aging is associated with pro-inflammatory and synaptic loss changes. Thus, comparable transcriptional regulatory networks that operate throughout the lifespan underlie different phenotypic processes during Aging compared to Development.

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Coordination of Gene Expression of Arachidonic and Docosahexaenoic Acid Cascade Enzymes during Human Brain Development and Aging

Cited by 25 publications

References 81 publications

Network pharmacology-based strategy to investigate pharmacological mechanisms of Ginkgo Biloba Extract for Aging

Network pharmacology-based strategy to investigate pharmacological mechanisms of Ginkgo Biloba Extract for Aging

Reconsidering Dietary Polyunsaturated Fatty Acids in Bipolar Disorder: A Translational Picture

Coordinated Gene Expression of Neuroinflammatory and Cell Signaling Markers in Dorsolateral Prefrontal Cortex during Human Brain Development and Aging

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