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https://www.readbyqxmd.com/read/28800615/pitx3-and-en1-determine-the-size-and-molecular-programming-of-the-dopaminergic-neuronal-pool
#1
Willemieke M Kouwenhoven, Lars von Oerthel, Marten P Smidt
Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral midbrain. These neurons form the substantia nigra (SNc) and the ventral tegmental area (VTA). Two transcription factors that play important roles in the process of terminal differentiation and subset-specification of mdDA neurons, are paired-like homeodomain transcription factor 3 (Pitx3), and homeobox transcription factor Engrailed 1 (En1). We previously investigated the single Pitx3KO and En1KO and observed important changes in the survival of mdDA neurons of the SNc and VTA as well as altered expression of pivotal rostral- and caudal-markers, Ahd2 and Cck, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28746897/parkinsonian-features-in-aging-gfap-hmox1-transgenic-mice-overexpressing-human-ho-1-in-the-astroglial-compartment
#2
Wei Song, Marisa Cressatti, Hillel Zukor, Adrienne Liberman, Carmela Galindez, Hyman M Schipper
Epigenetic influences mediating brain iron deposition, oxidative mitochondrial injury, and macroautophagy in Parkinson disease and related conditions remain enigmatic. Here, we show that selective overexpression of the stress protein, heme oxygenase-1 (HO-1) in astrocytes of GFAP.HMOX1 transgenic mice between 8.5 and 19 months of age results in nigrostriatal hypodopaminergia associated with locomotor incoordination and stereotypy; downregulation of tyrosine hydroxylase, DAT, LMX1B, Nurr1, Pitx3 and DJ-1 mRNA and/or protein; overproduction of α-synuclein and ubiquitin; oxidative stress; basal ganglia siderosis; mitochondrial damage/mitophagy; and augmented GABAergic systems (increased GABA, GAD67 and reelin)...
June 28, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28743636/valproate-increases-dopamine-transporter-expression-through-histone-acetylation-and-enhanced-promoter-binding-of-nurr1
#3
Ashley L Green, Le Zhan, Aseel Eid, Helmut Zarbl, Grace L Guo, Jason R Richardson
The dopamine transporter (DAT) is the key regulator of dopaminergic transmission and is a target of several xenobiotics, including pesticides and pharmacological agents. Previously, we identified a prominent role for histone deacetylases in the regulation of DAT expression. Here, we utilized a rat dopaminergic cell line (N27) to probe the responsiveness of DAT mRNA expression to inhibitors of histone acetylation. Inhibition of histone deacetylases (HDACs) by valproate, butyrate and Trichostatin A led to a 3-10-fold increase in DAT mRNA expression, a 50% increase in protein levels, which were accompanied by increased H3 acetylation levels...
July 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28685157/embryonic-development-of-selectively-vulnerable-neurons-in-parkinson-s-disease
#4
REVIEW
Miguel A P Oliveira, Rudi Balling, Marten P Smidt, Ronan M T Fleming
A specific set of brainstem nuclei are susceptible to degeneration in Parkinson's disease. We hypothesise that neuronal vulnerability reflects shared phenotypic characteristics that confer selective vulnerability to degeneration. Neuronal phenotypic specification is mainly the cumulative result of a transcriptional regulatory program that is active during the development. By manual curation of the developmental biology literature, we comprehensively reconstructed an anatomically resolved cellular developmental lineage for the adult neurons in five brainstem regions that are selectively vulnerable to degeneration in prodromal or early Parkinson's disease...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28598520/xenopus-pitx3-target-genes-lhx1-and-xnr5-are-identified-using-a-novel-three-fluor-flow-cytometry-based-analysis-of-promoter-activation-and-repression
#5
Lara N Hooker, Cristine Smoczer, Samuel Abbott, Mohamad Fakhereddin, John W Hudson, Michael J Crawford
BACKGROUND: Pitx3 plays a well understood role in directing development of lens, muscle fiber, and dopaminergic neurons; however, in Xenopus laevis, it may also play a role in early gastrulation and somitogenesis. Potential downstream targets of pitx3 possess multiple binding motifs that would not be readily accessible by conventional promoter analysis. RESULTS: We isolated and characterized pitx3 target genes lhx1 and xnr5 using a novel three-fluor flow cytometry tool that was designed to dissect promoters with multiple binding sites for the same transcription factor...
June 9, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28546921/a-novel-frameshift-mutation-in-cx46-associated-with-hereditary-dominant-cataracts-in-a-chinese-family
#6
Xiu-Kun Cui, Ke-Ke Zhu, Zheng Zhou, Si-Min Wan, Yi Dong, Xuan-Ce Wang, Jing Li, Jing Zhang, Hong-Mei Mu, Lei Qin, Yan-Zhong Hu
AIM: To investigate the genetic mutations that are associated the hereditary autosomal dominant cataract in a Chinese family. METHODS: A Chinese family consisting of 20 cataract patients (including 9 male and 11 female) and 2 unaffected individuals from 5 generations were diagnosed to be a typical autosomal dominant cataract pedigree. Genomic DNA samples were extracted from the peripheral blood cells of the participants in this pedigree. Exon sequence was used for genetic mutation screening...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28540026/meta-analysis-of-gwas-of-over-16-000-individuals-with-autism-spectrum-disorder-highlights-a-novel-locus-at-10q24-32-and-a-significant-overlap-with-schizophrenia
#7
(no author information available yet)
BACKGROUND: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28466092/repeated-social-defeat-and-the-rewarding-effects-of-cocaine-in-adult-and-adolescent-mice-dopamine-transcription-factors-probdnf-signaling-pathways-and-the-trkb-receptor-in-the-mesolimbic-system
#8
Sandra Montagud-Romero, Cristina Nuñez, M Carmen Blanco-Gandia, Elena Martínez-Laorden, María A Aguilar, Javier Navarro-Zaragoza, Pilar Almela, Maria-Victoria Milanés, María-Luisa Laorden, José Miñarro, Marta Rodríguez-Arias
RATIONALE: Repeated social defeat (RSD) increases the rewarding effects of cocaine in adolescent and adult rodents. OBJECTIVE: The aim of the present study was to compare the long-term effects of RSD on the conditioned rewarding effects of cocaine and levels of the transcription factors Pitx3 and Nurr1 in the ventral tegmental area (VTA), the dopamine transporter (DAT), the D2 dopamine receptor (D2DR) and precursor of brain-derived neurotrophic factor (proBDNF) signaling pathways, and the tropomyosin-related kinase B (TrkB) receptor in the nucleus accumbens (NAc) in adult and adolescent mice...
May 2, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28297587/efficiently-specified-ventral-midbrain-dopamine-neurons-from-human-pluripotent-stem-cells-under-xeno-free-conditions-restore-motor-deficits-in-parkinsonian-rodents
#9
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...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28249924/whole-exome-sequencing-identifies-a-novel-mutation-in-the-pitx3-gene-causing-autosomal-dominant-congenital-cataracts-in-a-chinese-family
#10
Hui Liu, Hankui Liu, Junxiang Tang, Qiongfen Lin, Yuxiu Sun, Chaohong Wang, Huanming Yang, Muhammad Riaz Khan, Mohamud Walid Peerbux, Sohail Ahmad, Ihtisham Bukhari, Jiansheng Zhu
BACKGROUND: Congenital cataract is the cloudiness of the eye's natural lens and is a primary cause of congenital vision loss. It accounts for almost 10% of childhood vision loss worldwide. METHODS: A four generation Chinese family having seven affected individuals was recruited for the current study. Exome sequencing was performed to identify the genetic cause of congenital cataract. RESULTS: Analysis of data identified a novel frameshift mutation, c...
January 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28174607/pitx3-dna-methylation-is-an-independent-predictor-of-overall-survival-in-patients-with-head-and-neck-squamous-cell-carcinoma
#11
Verena Sailer, Emily Eva Holmes, Heidrun Gevensleben, Diane Goltz, Freya Dröge, Alina Franzen, Jörn Dietrich, Glen Kristiansen, Friedrich Bootz, Andreas Schröck, Dimo Dietrich
BACKGROUND: Molecular biomarkers assisting risk-group assignment and subsequent treatment stratification are urgently needed for patients with squamous cell cancer of the head and neck region (HNSCC). Aberrant methylation is a frequent event in cancer and, therefore, a promising source for potential biomarkers. Here, the methylation status of the paired-like homeodomain transcription factor 3 (PITX3) was evaluated in HNSCC. METHODS: Using a quantitative real-time PCR, PITX3 methylation was assessed in a cohort of 326 HNSCC patients treated for localized or locally advanced disease (training cohort)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/27997829/redox-regulation-by-pitx2-and-pitx3-is-critical-for-fetal-myogenesis
#12
Aurore L'honoré, Pierre-Henri Commère, Jean-François Ouimette, Didier Montarras, Jacques Drouin, Margaret Buckingham
No abstract text is available yet for this article.
December 19, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27936186/maternal-separation-impairs-cocaine-induced-behavioural-sensitization-in-adolescent-mice
#13
Irene Gracia-Rubio, Elena Martinez-Laorden, Maria Moscoso-Castro, M Victoria Milanés, M Luisa Laorden, Olga Valverde
Adverse early-life conditions induce persistent disturbances that give rise to negative emotional states. Therefore, early life stress confers increased vulnerability to substance use disorders, mainly during adolescence as the brain is still developing. In this study, we investigated the consequences of maternal separation, a model of maternal neglect, on the psychotropic effects of cocaine and the neuroplasticity of the dopaminergic system. Our results show that mice exposed to maternal separation displayed attenuated behavioural sensitization, while no changes were found in the rewarding effects of cocaine in the conditioned place preference paradigm and in the reinforcing effects of cocaine in the self-administration paradigm...
2016: PloS One
https://www.readbyqxmd.com/read/27911668/association-of-5-hydroxymethylation-and-5-methylation-of-dna-cytosine-with-tissue-specific-gene-expression
#14
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 (5hmC) and 5-methylcytosine (5mC) at specific sites in these genes in skeletal muscle (SkM), myoblasts, heart, brain, and diverse other samples...
February 2017: 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
#15
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...
January 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/27844281/novel-neuroprotective-effects-of-melanin-concentrating-hormone-in-parkinson-s-disease
#16
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
#17
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
#18
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
#19
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
#20
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
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