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https://www.readbyqxmd.com/read/29416637/liver-x-receptors-agonist-promotes-differentiation-of-rat-bone-marrow-derived-mesenchymal-stem-cells-into-dopaminergic-neuron-like-cells
#1
Oumei Cheng, Xiaoyan Tian, Ying Luo, Shaoshan Mai, Yang Yang, Shengnan Kuang, Qi Chen, Jie Ma, Beibei Chen, Rong Li, Lu Yang, Huan Li, Congli Hu, Jiahua Zhang, Zhihao Chen, Yuke Li, Hui Xia, Ying Xu, Junqing Yang
Dopaminergic (DA) neurons derived from bone marrow derived mesenchymal stem cells (BMSCs) maybe a valuable source for cell replacement therapy in Parkinson disease. Recent studies showed that new functions of LXR and their ligands have been proposed to prevent PD in the adult nervous system. The present study was designed to observe the effect of liver X receptors (LXR) agonist on differentiation of rat BMSCs into DA neurons. Expressions of the neuronal markers (Tuj1 and Nestin), the specific marker of DA neurons (tyrosine hydroxylase, TH), LXR α and LXR β were measured by immunocytochemical assay and TH/Tuj1 positive cells were determined by quantitative cell count analyses...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29405783/identification-of-pitx3-mutations-in-individuals-with-various-ocular-developmental-defects
#2
Celia Zazo Seco, Julie Plaisancié, Tatiana Lupasco, Caroline Michot, Jacmine Pechmeja, Julian Delanne, Edouard Cottereau, Carmen Ayuso, Marta Corton, Patrick Calvas, Nicola Ragge, Nicolas Chassaing
BACKGROUND: Congenital cataract displays large phenotypic (syndromic and isolated cataracts) and genetic heterogeneity. Mutations in several transcription factors involved in eye development, like PITX3, have been associated with congenital cataracts and anterior segment mesenchymal disorders. MATERIALS AND METHODS: Targeted sequencing of 187 genes involved in ocular development was performed in 96 patients with mainly anophthalmia and microphthalmia. Additionally, Sanger sequencing analysis of PITX3 was performed on a second cohort of 32 index cases with congenital cataract and Peters anomaly and/or sclereocornea...
February 6, 2018: Ophthalmic Genetics
https://www.readbyqxmd.com/read/29404959/conserved-upstream-regulatory-regions-in-mammalian-tyrosine-hydroxylase
#3
Meng Wang, Lilah Fones, John W Cave
Tyrosine hydroxylase (Th) encodes the rate-limiting enzyme in catecholamine biosynthesis, and the regulation of its transcription is critical for the specification and maintenance of catecholaminergic neuron phenotypes. For many genes, regulatory genomic DNA sequences that are upstream of the proximal promoter control expression levels as well as region-specific expression patterns. The regulatory architecture of the genomic DNA upstream of the Th proximal promoter, however, is poorly understood. In this study, we examined the 11 kb upstream nucleotide sequence of Th from nine mammalian species and identified five highly conserved regions...
February 5, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29314435/mutation-update-of-transcription-factor-genes-foxe3-hsf4-maf-and-pitx3-causing-cataracts-and-other-developmental-ocular-defects
#4
Deepti Anand, Smriti A Agrawal, Anne Slavotinek, Salil A Lachke
Mutations in the transcription factor genes FOXE3, HSF4, MAF, and PITX3 cause congenital lens defects including cataracts that may be accompanied by defects in other components of the eye or in non-ocular tissues. We comprehensively describe here all the variants in FOXE3, HSF4, MAF, and PITX3 genes linked to human developmental defects. A total of 52 variants for FOXE3, 18 variants for HSF4, 20 variants for MAF, and 19 variants for PITX3 identified so far in isolated cases or within families are documented...
January 4, 2018: Human Mutation
https://www.readbyqxmd.com/read/29207913/generation-of-dopamine-secreting-cells-from-human-adipose-tissue-derived-stem-cells-in-vitro
#5
Mohammad Hasan Soheilifar, Arash Javeri, Hossein Amini, Masoumeh Fakhr Taha
Several studies have demonstrated the differentiation of human adipose tissue-derived stem cells (hADSCs) to neuronal and glial phenotypes, but directing the fate of these cells toward dopaminergic neurons has not been frequently reported. The aim of the present study was to investigate dopaminergic specification of hADSCs in vitro. ADSCs were isolated from subcutaneous abdominal adipose tissue and were characterized. For dopaminergic differentiation, a cocktail of sonic hedgehog, fibroblast growth factor 8, basic fibroblast growth factor and brain-derived neurotrophic factor were used under a low serum condition...
December 5, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/29163030/tcf12-is-involved-in-early-cell-fate-determination-and-subset-specification-of-midbrain-dopamine-neurons
#6
Simone Mesman, Marten P Smidt
The basic helix-loop-helix (bHLH) protein family has previously been shown to be involved in the development of mesodiencephalic dopaminergic (mdDA) neurons in the murine midbrain. Specifically, Ngn2 and Mash1 are known to have a role in the specification of neural progenitors in the ventricular zone (VZ) of the midbrain towards an mdDA neuronal cell-fate. Furthermore, other members of the bHLH protein family, the E-box factors, are expressed in the developing midbrain and are thought to have a role in neuronal differentiation...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28991698/pitx3-genotype-and-risk-of-dementia-in-parkinson-s-disease-a-population-based-study
#7
David Bäckström, Magdalena Eriksson Domellöf, Gabriel Granåsen, Jan Linder, Sofia Mayans, Eva Elgh, Susanna Jakobson Mo, Lars Forsgren
Dementia is a devastating manifestation of Parkinson's disease (PD). This study investigates whether a common polymorphism in the PITX3 gene (rs2281983), which is of importance for the function of dopaminergic neurons, affects the risk of developing dementia in PD and whether it affects dopamine transporter (DAT) uptake. We PITX3 genotyped 133 patients with new-onset, idiopathic PD, participating in a population-based study in Sweden. Patients were followed prospectively during 6-11years with extensive investigations, including neuropsychology and DAT-imaging with (123)I FP-CIT...
October 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28966651/impact-of-pitx3-gene-knockdown-on-glial-cell-line-derived-neurotrophic-factor-transcriptional-activity-in-dopaminergic-neurons
#8
Jing Chen, Xiao-Yu Kang, Chuan-Xi Tang, Dian-Shuai Gao
Pitx3 is strongly associated with the phenotype, differentiation, and survival of dopaminergic neurons. The relationship between Pitx3 and glial cell line-derived neurotrophic factor (GDNF) in dopaminergic neurons remains poorly understood. The present investigation sought to construct and screen a lentivirus expression plasmid carrying a rat Pitx3 short hairpin (sh)RNA and to assess the impact of Pitx3 gene knockdown on GDNF transcriptional activity in MES23.5 dopaminergic neurons. Three pairs of interference sequences were designed and separately ligated into GV102 expression vectors...
August 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28958789/expression-analyzes-of-early-factors-in-midbrain-differentiation-programs
#9
Simone Mesman, Sonja J Krüse, Marten P Smidt
Mesodiencephalic dopaminergic (mdDA) neurons are born in the ventricular zone (VZ) of the midbrain between E10 and E12. Although these neurons all express specific DA markers like Th and Pitx3, they are subdivided into distinct subsets, each depending on a unique set of transcription factors and signaling cascades for their differentiation. How a neural progenitor commits to an mdDA neuronal cell-fate and how the specification into the different subsets is determined remains unclear. To gain more insight into the development and specification of these neurons we have previously conducted a genome-wide expression analysis, in which dissected midbrain material (E10...
September 27, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28883785/early-postnatal-but-not-late-adult-neurogenesis-is-impaired-in-the-pitx3-mutant-animal-model-of-parkinson-s-disease
#10
Moritz D Brandt, Diana Krüger-Gerlach, Andreas Hermann, Anne K Meyer, Kwang-Soo Kim, Alexander Storch
The generation of new neurons in the adult dentate gyrus has functional implications for hippocampal formation. Reduced hippocampal neurogenesis has been described in various animal models of hippocampal dysfunction such as dementia and depression, which are both common non-motor-symptoms of Parkinson's disease (PD). As dopamine plays an important role in regulating precursor cell proliferation, the loss of dopaminergic neurons in the substantia nigra (SN) in PD may be related to the reduced neurogenesis observed in the neurogenic regions of the adult brain: subventricular zone (SVZ) and dentate gyrus (DG)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28875854/cytomegalovirus-infection-the-neurodevelopmental-peptide-signatures
#11
Guglielmo Lucchese, Darja Kanduc
BACKGROUND AND OBJECTIVE: HCMV infection may cause neurodevelopmental disorders, including intellectual disability, hearing loss, cortical malformations, and calcifications. Theorizing about the still unknown molecular basis of HCMV-related diseases, this study analyzes the peptide sharing between HCMV, strains AD169 and Merlin, and human proteins, searching for shared sequences that might lead to crossreactive autoimmune injuries in the brain during immune responses following HCMV infection...
August 29, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28871128/synergistic-effect-of-bdnf-and-fgf2-in-efficient-generation-of-functional-dopaminergic-neurons-from-human-mesenchymal-stem-cells
#12
Manisha Singh, Anupama Kakkar, Rinkey Sharma, O P Kharbanda, Nitika Monga, Manish Kumar, Shantanu Chowdhary, Balram Airan, Sujata Mohanty
To understand the process of neurogenesis, generation of functional dopaminergic (DAergic) neurons from human mesenchymal stem cells (hMSCs) is important. BDNF has been reported to be responsible for inducing neuronal maturation and functionality. Previously, we have reported the efficient generation of neurons from human bone marrow derived MSCs using FGF2 alone. We hypothesize that hMSCs from various tissues [(bone marrow (BM), adipose tissue (AD) and dental pulp (DP)], if treated with BDNF on 9(th) day of induction, alongwith FGF2 will generate functional DAergic neurons...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28867345/a-pitx3-egfp-reporter-line-reveals-connectivity-of-dopamine-and-non-dopamine-neuronal-subtypes-in-grafts-generated-from-human-embryonic-stem-cells
#13
Jonathan C Niclis, Carlos W Gantner, Cameron P J Hunt, Jessica A Kauhausen, Jennifer C Durnall, John M Haynes, Colin W Pouton, Clare L Parish, Lachlan H Thompson
Development of safe and effective stem cell-based therapies for brain repair requires an in-depth understanding of the in vivo properties of neural grafts generated from human stem cells. Replacing dopamine neurons in Parkinson's disease remains one of the most anticipated applications. Here, we have used a human PITX3-EGFP embryonic stem cell line to characterize the connectivity of stem cell-derived midbrain dopamine neurons in the dopamine-depleted host brain with an unprecedented level of specificity. The results show that the major A9 and A10 subclasses of implanted dopamine neurons innervate multiple, developmentally appropriate host targets but also that the majority of graft-derived connectivity is non-dopaminergic...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28831020/niche-derived-laminin-511-promotes-midbrain-dopaminergic-neuron-survival-and-differentiation-through-yap
#14
Dawei Zhang, Shanzheng Yang, Enrique M Toledo, Daniel Gyllborg, Carmen Saltó, J Carlos Villaescusa, Ernest Arenas
Parkinson's disease (PD) is a neurodegenerative disorder in which the loss of dopaminergic neurons in the midbrain (mDA neurons) causes progressive loss of motor control and function. Using embryonic and mDA neurons, midbrain tissue from mice, and differentiated human neural stem cells, we investigated the mechanisms controlling the survival of mDA neurons. We found that the extracellular matrix protein laminin-511 (LM511) promoted the survival and differentiation of mDA neurons. LM511 bound to integrin α3β1 and activated the transcriptional cofactor YAP...
August 22, 2017: Science Signaling
https://www.readbyqxmd.com/read/28800615/pitx3-and-en1-determine-the-size-and-molecular-programming-of-the-dopaminergic-neuronal-pool
#15
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
#16
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
#17
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...
October 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28685157/embryonic-development-of-selectively-vulnerable-neurons-in-parkinson-s-disease
#18
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
#19
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
#20
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
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