Epigenetic regulation of astrocyte function in neuroinflammation and neurodegeneration

Neal, Matthew; Richardson, Jason R.

doi:10.1016/j.bbadis.2017.11.004

Cited by 129 publications

(96 citation statements)

References 196 publications

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“…[57][58][59][60] Alteration of DNA methylation has been implicated in We observed that WMI induced methylation perturbation in a period highly important for neurodevelopment that persisted up to 21 days post-injury.…”

Section: Discussionmentioning

confidence: 79%

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Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups

et al. 2019

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This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. contributed equally to this study.Abbreviations: ASD, autism spectrum disorder; CpG, cytosine followed by guanine; DMR, differentially methylated region; DOHaD, developmental origins of health and disease; E. coli, Escherichia coli; GO, gene ontology; LPS, lipopolysaccharide; P3, postnatal day 3; P4, postnatal day 4; P24, postnatal day 24; PBS, phosphate-buffered saline; PFA, paraformaldehyde; RRBS, reduced representation bisulfite sequencing; WMI, white matter injury. AbstractPreterm infants are vulnerable to inflammation-induced white matter injury (WMI), which is associated with neurocognitive impairment and increased risk of neuropsychiatric diseases in adulthood. Epigenetic mechanisms, particularly DNA methylation, play a role in normal development and modulate the response to pathological challenges. Our aims were to determine how WMI triggered DNA methylation alterations in brains of neonatal rats and if such changes persisted over time. We used a robust model of WMI by injecting lipopolysaccharide (LPS) or sterile saline in the corpus callosum of 3-day-old (P3) rat pups. Brains were collected 24 hours (P4) and 21 days post-injection (P24). We extracted genomic DNA from the brain to establish genome-wide quantitative DNA methylation profiles using reduced representation bisulfite sequencing. Neonatal LPS exposure induced a persistent increased methylation of genes related to nervous system development and a reduced methylation of genes associated with inflammatory pathways. These findings suggest that early-life neuroinflammatory exposure impacts the cerebral methylation landscape with determining widespread epigenetic modifications especially in genes related to neurodevelopment. K E Y W O R D SDNA methylation, epigenetics, lipopolysaccharide, periventricular leukomalacia

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Section: Discussionmentioning

confidence: 79%

“…DNA methylation is an important regulatory mechanism that partakes in neurodevelopmental processes, different neurological functions such as learning and memory and maintenance of homeostasis at adulthood. [57][58][59][60] Alteration of DNA methylation has been implicated in…”

Section: Discussionmentioning

confidence: 99%

Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups

et al. 2019

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“…; Chitnis and Weiner ; Labzin et al . ; Fehily and Fitzgerald ; Mizuma and Yenari ; Neal and Richardson ; Franklin et al . ; Prata et al .…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

“…The disorders considered in the present review are caused by different etiologic factors and display a variety of symptoms that could hardly be reconducted to a unifying pattern. However, regardless of the origin of these diseases, the involvement of processes which share aspects reasonably attributable to inflammation is detectable in their underlying pathogenic mechanisms (Giovannoni et al 2007;Wilcock and Griffin 2013;King et al 2014;Ochoa-Cortes et al 2016;Hamlett et al 2018;Stark et al 2016;Chitnis and Weiner 2017;Labzin et al 2018;Fehily and Fitzgerald 2017;Mizuma and Yenari 2017;Neal and Richardson 2017;Franklin et al 2017;Prata et al 2017;Santos and Ferreira 2017;Joshi and Singh 2017;Thelin et al 2017a;Majd et al 2017;Zhang et al 2017;Zolezzi and Inestrosa 2017). This consideration has also been the object of a recent valuable review (Skaper et al 2018).…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

The S100B story: from biomarker to active factor in neural injury

Michetti

D’Ambrosi

Toesca

et al. 2018

Journal of Neurochemistry

273

238

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S100B is a Ca -binding protein mainly concentrated in astrocytes. Its levels in biological fluids (cerebrospinal fluid, peripheral and cord blood, urine, saliva, amniotic fluid) are recognized as a reliable biomarker of active neural distress. Although the wide spectrum of diseases in which the protein is involved (acute brain injury, neurodegenerative diseases, congenital/perinatal disorders, psychiatric disorders) reduces its specificity, its levels remain an important aid in monitoring the trend of the disorder. Mounting evidence now points to S100B as a Damage-Associated Molecular Pattern molecule which, when released at high concentration, through its Receptor for Advanced Glycation Endproducts, triggers tissue reaction to damage in a series of different neural disorders. This review addresses this novel scenario, presenting data indicating that S100B levels and/or distribution in the nervous tissue of patients and/or experimental models of different neural disorders, for which the protein is used as a biomarker, are directly related to the progress of the disease: acute brain injury (ischemic/hemorrhagic stroke, traumatic injury), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis), congenital/perinatal disorders (Down syndrome, spinocerebellar ataxia-1), psychiatric disorders (schizophrenia, mood disorders), inflammatory bowel disease. In many cases, over-expression/administration of the protein induces worsening of the disease, whereas its deletion/inactivation produces amelioration. This review points out that the pivotal role of the protein resulting from these data, opens the perspective that S100B may be regarded as a therapeutic target for these different diseases, which appear to share some common features reasonably attributable to neuroinflammation, regardless their origin.

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“…Neurodegenerative diseases are characterised by a progressive decline in neuronal health ultimately leading to cell death. Alzheimer's (AD), Parkinson's (PD) and Huntington's diseases are increasingly prevalent neurological conditions that share several common pathways including neuroinflammation, enhanced oxidative stress, metabolic dysfunction and most importantly, the accumulation of misfolded proteins [1][2][3]. One particular form of neuronal degeneration caused by propagating protein misfolding is prion disease, a fatal, progressive neurodegenerative disorder characterised by an accumulation and aggregation of misfolded scrapie-like prion protein PrP Sc [4,5].…”

Section: Mainmentioning

confidence: 99%

Alterations in neuronal metabolism contribute to the pathogenesis of prion disease

et al. 2018

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Neurodegenerative conditions are characterised by a progressive loss of neurons, which is believed to be initiated by misfolded protein aggregations. During this time period, many physiological and metabolomic alterations and changes in gene expression contribute to the decline in neuronal function. However, these pathological effects have not been fully characterised. In this study, we utilised a metabolomic approach to investigate the metabolic changes occurring in the hippocampus and cortex of mice infected with misfolded prion protein. In order to identify these changes, the samples were analysed by ultrahigh-performance liquid chromatography-tandem mass spectroscopy. The present dataset comprises a total of 498 compounds of known identity, named biochemicals, which have undergone principal component analysis and supervised machine learning. The results generated are consistent with the prion-inoculated mice having significantly altered metabolic profiles. In particular, we highlight the alterations associated with the metabolism of glucose, neuropeptides, fatty acids, L-arginine/nitric oxide and prostaglandins, all of which undergo significant changes during the disease. These data provide possibilities for future studies targeting and investigating specific pathways to better understand the processes involved in neuronal dysfunction in neurodegenerative diseases.

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Epigenetic regulation of astrocyte function in neuroinflammation and neurodegeneration

Cited by 129 publications

References 196 publications

Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups

Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups

The S100B story: from biomarker to active factor in neural injury

Alterations in neuronal metabolism contribute to the pathogenesis of prion disease

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