Developmental lead exposure and lifespan alterations in epigenetic regulators and their correspondence to biomarkers of Alzheimer's disease

Eid, Aseel; Bihaqi, Syed Waseem; Renehan, William E.; Zawia, Nasser H.

doi:10.1016/j.dadm.2016.02.002

Cited by 70 publications

(49 citation statements)

References 32 publications

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“…In our cell culture studies, Ab 42 promoted a decrease in the nuclear levels of DNMT1, although DNMT3a and DNMT3b were unaffected. Cerebral levels of DNMT1 have been shown to be reduced in AD mouse models (62,63). However, we did not observe a decrease in the methylation of the RELN promoter, either in frontal cortex from patients with AD or in our cell culture studies.…”

Section: Discussioncontrasting

confidence: 89%

Decreased generation of C‐terminal fragments of ApoER2 and increased reelin expression in Alzheimer's disease

et al. 2018

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Increasing evidence indicates that altered reelin signaling could contribute to synaptic dysfunction in Alzheimer's disease (AD). We found that reelin protein and mRNA levels were increased in the AD brain (particularly at advanced Braak stages in apolipoprotein E4 noncarriers), compared with that of control subjects. The β-amyloid (Aβ) protein impairs reelin activity and increases reelin expression through a mechanism that is not yet understood. To explore that mechanism, we examined the effect of Aβ aa 1-42 (Aβ) on DNA methylation of the RELN promoter and the processing of reelin receptor apolipoprotein E receptor 2 (ApoER2) in differentiated SH-SY5Y cells because ApoER2 C-terminal fragments (CTFs), generated after reelin binding, regulate reelin expression. We found that Aβ decreased nuclear levels of DNA-methyltransferase 1. However, RELN promoter methylation did not change in Aβ-treated cells or in AD brain extracts. Instead, the levels of ApoER2-CTF appeared significantly lower in Aβ-treated cells and in AD extracts from advanced Braak stages of apolipoprotein E4 noncarriers. Our data show that ApoER2-CTF levels are decreased, whereas reelin expression is increased in AD brain at advanced Braak stages and after Aβ treatment, supporting the view that ApoER2-CTF exerts a modulatory role on reelin expression.-Mata-Balaguer, T., Cuchillo-Ibañez, I., Calero, M., Ferrer, I., Sáez-Valero, J. Decreased generation of C-terminal fragments of ApoER2 and increased reelin expression in Alzheimer's disease.

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Section: Discussioncontrasting

confidence: 89%

Decreased generation of C‐terminal fragments of ApoER2 and increased reelin expression in Alzheimer's disease

et al. 2018

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“…The current study was performed to extend these findings by examining the extent to which Pb, PS and Pb + PS affects levels of other post-translational histone modifications (PTHMs) H3K9Ac, H3K4Me3 (activating marks) and H3K9Me2 and H3K27Me3 (repressive marks) in FC and HIPP during fetal development (E18), early postnatal life (PND0, PND6) and in adulthood (PND60) in males and females. These PTHMs were chosen for study as they have been associated with cognitive functioning (Peixoto and Abel, 2013; Parkel et al, 2013; Jarome et al, 2014), environment exposures (Hou et al, 2012; Eid et al, 2016), postnatal stress (Weaver et al, 2004) and may be differentially regulated in males and females (McCarthy et al, 2009; Shen et al, 2015; McCarthy and Nugent, 2015). These specific PTHMs have not been previously studied in the context of Pb exposure and PS.…”

Section: Introductionmentioning

confidence: 99%

Sex- and brain region- specific effects of prenatal stress and lead exposure on permissive and repressive post-translational histone modifications from embryonic development through adulthood

et al. 2017

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Developmental exposure to prenatal stress (PS) and lead (Pb) can affect brain development and adversely influence behavior and cognition. Epigenetic-based gene regulation is crucial for normal brain development and mis-regulation, in any form, can result in neurodevelopmental disorders. Post-translational histone modifications (PTHMs) are an integral and dynamic component of the epigenetic machinery involved in gene regulation. Exposures to Pb and/or PS may alter PTHM profiles, promoting lifelong alterations in brain function observed following Pb ± PS exposure. Here we examined the effects of Pb ± PS on global levels of activating marks H3K9Ac and H3K4Me3 and repressive marks H3K9Me2 and H3K27Me3 at different developmental stages: E18, PND0, PND6 and PND60. Dams were exposed to 0 or 100 ppm Pb beginning 2 months prior to breeding followed by no PS (NS) or PS resulting in 4 offspring treatment groups per sex: 0-NS (control), 0-PS, 100-NS and 100-PS. Global levels of PTHMs varied from E18 through adulthood even in control mice, and were influenced by sex and brain-region. The developmental trajectory of these PTHM levels was further modified by Pb ± PS in a sex-, brain region-and age-dependent manner. Females showed a preferential response to Pb alone in frontal cortex (FC) and differentially to PS alone and combined Pb + PS in hippocampus (HIPP). In males, PS-induced increases in PTHM levels in FC, whereas PS produced reductions in HIPP. Pb ± PS-based changes in PTHM levels continued to be observed in adulthood (PND60), demonstrating the la sting effect of these early life environmental events on these histone marks. These results indicate that epigenetic consequences of Pb ± PS and their contribution to mechanisms of toxicity are sex dependent. Additional studies will assist in understanding the functional significance of these changes in PTHM levels on expression of individual genes, functional pathways, and ultimately, their behavioral consequences.

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“…İfadesi artan genlerin DNA hipometilasyonu ile ilişkili olabileceği ancak azalan genlerin ifadesinin histon modifikasyonlarına (H3K9Ac, H3K4me2, H3K27me3) bağlı olabileceği öngörülmüştür. 35 DNA hipometilasyonu çoğunlukla yer değiş-tirebilen Alu, LINE gibi tekrarlanan DNA dizilerinde belirlenmiştir. Retrotranspozon adı verilen yer değiştirebilen DNA tekrar dizileri gen düzen-lenmesi ve genom stabilitesinde önemli role sahiptir.…”

Section: Dna Meti̇lasyon Deği̇şi̇mleri̇ Ve Yaşlanmaunclassified

Epigenetic Alterations in Aging and Aging-Associated Diseases: Review

Güneş¹,

Bayramov²

2016

Turkiye Klinikleri J Med Sci

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Developmental lead exposure and lifespan alterations in epigenetic regulators and their correspondence to biomarkers of Alzheimer's disease

Cited by 70 publications

References 32 publications

Decreased generation of C‐terminal fragments of ApoER2 and increased reelin expression in Alzheimer's disease

Decreased generation of C‐terminal fragments of ApoER2 and increased reelin expression in Alzheimer's disease

Sex- and brain region- specific effects of prenatal stress and lead exposure on permissive and repressive post-translational histone modifications from embryonic development through adulthood

Epigenetic Alterations in Aging and Aging-Associated Diseases: Review

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