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https://www.readbyqxmd.com/read/27911668/association-of-5-hydroxymethylation-and-5-methylation-of-dna-cytosine-with-tissue-specific-gene-expression
#1
V K Chaithanya Ponnaluri, Kenneth C Ehrlich, Guoqiang Zhang, Michelle Lacey, Douglas Johnston, Sriharsa Pradhan, Melanie Ehrlich
Differentially methylated or hydroxymethylated regions (DMRs) in mammalian DNA are often associated with tissue-specific gene expression but the functional relationships are still being unraveled. To elucidate these relationships, we studied 16 human genes containing myogenic DMRs by analyzing profiles of their epigenetics and transcription and quantitatively assaying 5-hydroxymethylcytosine (5 hmC) and 5-methylcytosine (5 mC) at specific sites in these genes in skeletal muscle (SkM), myoblasts, heart, brain, and diverse other samples...
December 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27845051/intrinsic-lens-potential-of-neural-retina-inhibited-by-notch-signaling-as-the-cause-of-lens-transdifferentiation
#2
Hideaki Iida, Yasuo Ishii, Hisato Kondoh
Embryonic neural retinas of avians produce lenses under spreading culture conditions. This phenomenon has been regarded as a paradigm of transdifferentiation due to the overt change in cell type. Here we elucidated the underlying mechanisms. Retina-to-lens transdifferentiation occurs in spreading cultures, suggesting that it is triggered by altered cell-cell interactions. Thus, we tested the involvement of Notch signaling based on its role in retinal neurogenesis. Starting from E8 retina, a small number of crystallin-expressing lens cells began to develop after 20 days in control spreading cultures...
November 11, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27844281/novel-neuroprotective-effects-of-melanin-concentrating-hormone-in-parkinson-s-disease
#3
Ji-Yeun Park, Seung-Nam Kim, Junsang Yoo, Jaehwan Jang, Ahreum Lee, Ju-Young Oh, Hongwon Kim, Seung Tack Oh, Seong-Uk Park, Jongpil Kim, Hi-Joon Park, Songhee Jeon
Acupuncture has shown the therapeutic effect on various neurodegenerative disorders including Parkinson's disease (PD). While investigating the neuroprotective mechanism of acupuncture, we firstly found the novel function of melanin-concentrating hormone (MCH) as a potent neuroprotective candidate. Here, we explored whether hypothalamic MCH mediates the neuroprotective action of acupuncture. In addition, we aimed at evaluating the neuroprotective effects of MCH and elucidating underlying mechanism in vitro and in vivo PD models...
November 14, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27742845/efficiently-specified-ventral-midbrain-dopamine-neurons-from-human-pluripotent-stem-cells-under-xeno-free-conditions-restore-motor-deficits-in-parkinsonian-rodents
#4
Jonathan C Niclis, Carlos W Gantner, Walaa F Alsanie, Stuart J McDougall, Chris R Bye, Andrew G Elefanty, Edouard G Stanley, John M Haynes, Colin W Pouton, Lachlan H Thompson, Clare L Parish
: : Recent studies have shown evidence for the functional integration of human pluripotent stem cell (hPSC)-derived ventral midbrain dopamine (vmDA) neurons in animal models of Parkinson's disease. Although these cells present a sustainable alternative to fetal mesencephalic grafts, a number of hurdles require attention prior to clinical translation. These include the persistent use of xenogeneic reagents and challenges associated with scalability and storage of differentiated cells. In this study, we describe the first fully defined feeder- and xenogeneic-free protocol for the generation of vmDA neurons from hPSCs and utilize two novel reporter knock-in lines (LMX1A-eGFP and PITX3-eGFP) for in-depth in vitro and in vivo tracking...
October 14, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27708722/pitx3-promoter-methylation-is-a-prognostic-biomarker-for-biochemical-recurrence-free-survival-in-prostate-cancer-patients-after-radical-prostatectomy
#5
Emily Eva Holmes, Diane Goltz, Verena Sailer, Maria Jung, Sebastian Meller, Barbara Uhl, Jörn Dietrich, Magda Röhler, Jörg Ellinger, Glen Kristiansen, Dimo Dietrich
BACKGROUND: Molecular biomarkers that might help to distinguish between more aggressive and clinically insignificant prostate cancers (PCa) are still urgently needed. Aberrant DNA methylation as a common molecular alteration in PCa seems to be a promising source for such biomarkers. In this study, PITX3 DNA methylation (mPITX3) and its potential role as a prognostic biomarker were investigated. Furthermore, mPITX3 was analyzed in combination with the established PCa methylation biomarker PITX2 (mPITX2)...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27704331/admixing-of-mptp-resistant-and-susceptible-mice-strains-augments-nigrostriatal-neuronal-correlates-to-resist-mptp-induced-neurodegeneration
#6
D J Vidyadhara, H Yarreiphang, T R Raju, Phalguni Anand Alladi
Disease genetics in admixed populations like Hispanic-Americans, African-Americans, etc. are gaining importance due to high disease burden in them. Furthermore, epidemiological studies conclusively prove ethnicity-based differential prevalence of Parkinson's disease (PD), since the American-Caucasians are more susceptible than Asian-Indians and Africans. Contradictorily, Anglo-Indians, an admixture of Europeans and Asian-Indians are five-times less susceptible than Indians. We evaluated the neural basis of this phenomenon using the cytomorphological features of susceptibility to nigrostriatal neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
October 4, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27580818/folr1-a-novel-cell-surface-marker-for-isolating-midbrain-dopamine-neural-progenitors-and-nascent-dopamine-neurons
#7
Nicole Gennet, Claudia Tamburini, Xinsheng Nan, Meng Li
Cell type-specific surface markers offer a powerful tool for purifying defined cell types for restorative therapies and drug screenings. Midbrain dopaminergic neurons (mesDA) are the nerve cells preferentially lost in the brains of Parkinson's disease patients. Clinical trials of transplantation of fetal neural precursors suggest that cell therapy may offer a cure for this devastating neurological disease. Many lines of preclinical studies demonstrate that neural progenitors committed to dopaminergic fate survive and integrate better than postmitotic DA neurons...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27514757/specificity-of-pitx3-dependent-gene-regulatory-networks-in-subsets-of-midbrain-dopamine-neurons
#8
Panojot Bifsha, Aurelio Balsalobre, Jacques Drouin
Dysfunction of midbrain dopaminergic (mDA) neurons is involved in Parkinson's disease (PD) and neuropsychiatric disorders. Pitx3 is expressed in mDA neuron subsets of the substantia nigra compacta (SNc) and of the ventral tegmental area (VTA) that are degeneration-sensitive in PD. The genetic network(s) and mode(s) of action of Pitx3 in these mDA neurons remain poorly characterized. We hypothesized that, given their distinct neuronal identities, Pitx3-expressing neurons of SNc and VTA should differ in their Pitx3-controlled gene expression networks and this may involve subset-specific co-regulators...
August 11, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27513680/effects-of-simazine-exposure-on-neuronal-development-related-factors-in-mn9d-cells
#9
Jia Yu, Xueting Li, Junwei Yang, Yanping Wu, Baixiang Li
BACKGROUND Simazine is a triazine herbicide used worldwide in both agricultural and non-agricultural fields that is frequently detected in surface water and groundwater. Due to its widespread use, an increasing amount of research has focused on the potentially serious environmental and health risks. MATERIAL AND METHODS We used Western blotting and real-time quantitative PCR to analyze the effects of simazine on dopamine neuronal development-related factors in MN9D dopaminergic cells. RESULTS The expression of tyrosine hydroxylase (TH) mRNA was significantly increased after treatment with 300 and 600 μmol L-1 simazine after 24 and 48 h...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27512998/re-cloning-the-n27-dopamine-cell-line-to-improve-a-cell-culture-model-of-parkinson-s-disease
#10
Lu Gao, Wenbo Zhou, Breanna Symmes, Curt R Freed
Parkinson's disease is characterized by the death of dopaminergic neurons in the substantia nigra. To understand the molecular mechanisms of the disease, an in vitro model is important. In the 1990s, we used the SV40 large T antigen to immortalize dopaminergic neurons derived from Embryonic Day 14 rat mesencephalon. We selected a clone for its high expression of dopaminergic neuron markers such as tyrosine hydroxylase (TH), and we named it 1RB3AN27 (N27). Because the original N27 cell line has been passaged many times, the line has become a mixture of cell types with highly variable expression of TH...
2016: PloS One
https://www.readbyqxmd.com/read/27415467/dna-methylome-changes-by-estradiol-benzoate-and-bisphenol-a-links-early-life-environmental-exposures-to-prostate-cancer-risk
#11
Ana Cheong, Xiang Zhang, Yuk-Yin Cheung, Wan-Yee Tang, Jing Chen, Shu-Hua Ye, Mario Medvedovic, Yuet-Kin Leung, Gail S Prins, Shuk-Mei Ho
Developmental exposure to endocrine-disrupting chemicals (EDCs), 17β-estradiol-3-benzoate (EB) and bisphenol A (BPA), increases susceptibility to prostate cancer (PCa) in rodent models. Here, we used the methylated-CpG island recovery assay (MIRA)-assisted genomic tiling and CpG island arrays to identify treatment-associated methylome changes in the postnatal day (PND)90 dorsal prostate tissues of Sprague-Dawley rats neonatally (PND1, 3, and 5) treated with 25 µg/pup or 2,500 µg EB/kg body weight (BW) or 0...
July 14, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27354364/a-pbx1-transcriptional-network-controls-dopaminergic-neuron-development-and-is-impaired-in-parkinson-s-disease
#12
J Carlos Villaescusa, Bingsi Li, Enrique M Toledo, Pia Rivetti di Val Cervo, Shanzheng Yang, Simon Rw Stott, Karol Kaiser, Saiful Islam, Daniel Gyllborg, Rocio Laguna-Goya, Michael Landreh, Peter Lönnerberg, Anna Falk, Tomas Bergman, Roger A Barker, Sten Linnarsson, Licia Selleri, Ernest Arenas
Pre-B-cell leukemia homeobox (PBX) transcription factors are known to regulate organogenesis, but their molecular targets and function in midbrain dopaminergic neurons (mDAn) as well as their role in neurodegenerative diseases are unknown. Here, we show that PBX1 controls a novel transcriptional network required for mDAn specification and survival, which is sufficient to generate mDAn from human stem cells. Mechanistically, PBX1 plays a dual role in transcription by directly repressing or activating genes, such as Onecut2 to inhibit lateral fates during embryogenesis, Pitx3 to promote mDAn development, and Nfe2l1 to protect from oxidative stress...
September 15, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27208834/efficient-generation-of-dopaminergic-like-neurons-by-overexpression-of-nurr1-and-pitx3-in-mouse-induced-pluripotent-stem-cells
#13
Salemeh Salemi, Parvaneh Baktash, Bahareh Rajaei, Mehri Noori, Hossein Amini, Mehdi Shamsara, Mohammad Massumi
Parkinson's disease (PD) is a neurodegenerative disorder, in which the nigro-striatal Dopaminergic (DAergic) neurons are selectively lost. Treatment of neurodegenerative diseases with Pluripotent Stem Cells (PSCs) is a big interest in cell therapy. Here, we used induced Pluripotent Stem Cells (iPSCs) expressing two master Dopaminergic (DAergic) transcription factors, i.e. Nurr1 and Pitx3, to generate functional in vitro DAergic-like neurons. After establishment and characterization of Doxycycline-inducible iPSCs from mouse fibroblasts, the cells were transduced by NURR1- and PITX3-harboring lentiviruses...
July 28, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27145793/genetic-analysis-of-pitx3-variants-in-patients-with-essential-tremor
#14
H Chen, Z Song, L Yuan, W Xiong, Z Yang, L Gong, H Deng
BACKGROUND: A clinical overlap between essential tremor (ET) and Parkinson's disease (PD) has prompted investigation whether these disorders share common genetic factors. The paired-like homeodomain transcription factor 3 gene (PITX3) has been shown to play an important role for the differentiation and survival of midbrain dopaminergic neurons in the substantia nigra pars compacta. The preferential degeneration of those dopaminergic neurons is the pathological hallmark in PD. AIMS OF THE STUDY: The purpose of this study was to evaluate whether PITX3 variants are related to susceptibility of ET in Chinese Han population...
May 4, 2016: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/26992779/systems-biology-of-lens-development-a-paradigm-for-disease-gene-discovery-in-the-eye
#15
Deepti Anand, Salil A Lachke
Over the past several decades, the biology of the developing lens has been investigated using molecular genetics-based approaches in various vertebrate model systems. These efforts, involving target gene knockouts or knockdowns, have led to major advances in our understanding of lens morphogenesis and the pathological basis of cataracts, as well as of other lens related eye defects. In particular, we now have a functional understanding of regulators such as Pax6, Six3, Sox2, Oct1 (Pou2f1), Meis1, Pnox1, Zeb2 (Sip1), Mab21l1, Foxe3, Tfap2a (Ap2-alpha), Pitx3, Sox11, Prox1, Sox1, c-Maf, Mafg, Mafk, Hsf4, Fgfrs, Bmp7, and Tdrd7 in this tissue...
March 15, 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/26881122/neuroprotective-transcription-factors-in-animal-models-of-parkinson-disease
#16
REVIEW
François-Xavier Blaudin de Thé, Hocine Rekaik, Alain Prochiantz, Julia Fuchs, Rajiv L Joshi
A number of transcription factors, including En1/2, Foxa1/2, Lmx1a/b, Nurr1, Otx2, and Pitx3, with key roles in midbrain dopaminergic (mDA) neuron development, also regulate adult mDA neuron survival and physiology. Mouse models with targeted disruption of some of these genes display several features reminiscent of Parkinson disease (PD), in particular the selective and progressive loss of mDA neurons in the substantia nigra pars compacta (SNpc). The characterization of these animal models has provided valuable insights into various mechanisms of PD pathogenesis...
2016: Neural Plasticity
https://www.readbyqxmd.com/read/26873632/role-of-aromatase-and-radial-glial-cells-in-neurotoxin-induced-dopamine-neuron-degeneration-and-regeneration
#17
Lei Xing, Maddie J Venables, Vance L Trudeau
Radial glial cells (RGCs) in teleost brain are progenitor cells that express aromatase B and produce estrogens. Controversial data suggest that estrogens are critical for brain repair and neurogenesis in teleosts. Using a goldfish model for neurotoxin-induced Parkinson-like syndrome, we investigated the possible roles of RGCs, especially estrogen synthetic function, in the processes underlying dopamine neuron regeneration. The data indicate that dopamine neuron degeneration and aromatase activity inhibition could be respectively achieved in vivo with treatments with the neurotoxin 1-methyl-1,2,3,6-tetrahydropyridine (MPTP) and fadrozole in female goldfish...
February 9, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/26773559/differential-neuronal-plasticity-of-dental-pulp-stem-cells-from-exfoliated-deciduous-and-permanent-teeth-towards-dopaminergic-neurons
#18
Debanjana Majumdar, Mohammad Kanafi, Ramesh Bhonde, Pawan Gupta, Indrani Datta
Based on early occurrence in chronological age, stem-cells from human exfoliated deciduous teeth (SHED) has been reported to possess better differentiation-potential toward certain cell-lineage in comparison to stem-cells from adult teeth (DPSCs). Whether this same property between them extends for the yield of functional central nervous system neurons is still not evaluated. Hence, we aim to assess the neuronal plasticity of SHED in comparison to DPSCs toward dopaminergic-neurons and further, if the difference is reflected in a differential expression of sonic-hedgehog (SHH)-receptors and basal-expressions of tyrosine-hydroxylase [TH; through cAMP levels]...
September 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/26678495/role-of-nurr1-in-the-generation-and-differentiation-of-dopaminergic-neurons-from-stem-cells
#19
Eva Rodríguez-Traver, Oscar Solís, Eva Díaz-Guerra, Óscar Ortiz, Eva Vergaño-Vera, Héctor R Méndez-Gómez, Patricia García-Sanz, Rosario Moratalla, Carlos Vicario-Abejón
NURR1 is an essential transcription factor for the differentiation, maturation, and maintenance of midbrain dopaminergic neurons (DA neurons) as it has been demonstrated using knock-out mice. DA neurons of the substantia nigra pars compacta degenerate in Parkinson's disease (PD) and mutations in the Nurr1 gene have been associated with this human disease. Thus, the study of NURR1 actions in vivo is fundamental to understand the mechanisms of neuron generation and degeneration in the dopaminergic system. Here, we present and discuss findings indicating that NURR1 is a valuable molecular tool for the in vitro generation of DA neurons which could be used for modeling and studying PD in cell culture and in transplantation approaches...
July 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/26593886/from-eyeless-to-neurological-diseases
#20
Jochen Graw
Age-related cataracts are frequently associated with degenerative changes in the ocular lens including the aggregation of proteins - mainly crystallins, but also other proteins including amyloids (Aβ) leading to the hypothesis that cataracts could be used as "biomarkers" for Alzheimer disease. Even if this hypothesis was rejected by David Beebe's last paper (Bei et al., Exp. Eye Res., in press), it is a fascinating aspect to look for commonalities between eye diseases and neurological disorders. In this review, I discuss such commonalities between eye and brain mainly from a developmental point of view...
November 22, 2015: Experimental Eye Research
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