Generation of induced dopaminergic (iDA) neurons may provide a significant step forward towards cell replacement therapy for Parkinson's disease (PD). To study and compare transcriptional programs of induced cells versus primary DA neurons is a preliminary step towards characterizing human iDA neurons. We have optimized a protocol to efficiently generate iDA neurons from human pluripotent stem cells (hPSCs). We then sequenced the transcriptomes of iDA neurons derived from 6 different hPSC lines and compared them to that of primary midbrain (mDA) neurons. We identified a small subset of genes with altered expression in derived iDA neurons from patients with Parkinson's Disease (PD). We also observed that iDA neurons differ significantly from primary mDA neurons in global gene expression, especially in genes related to neuron maturation level. Results suggest iDA neurons from patient iPSCs could be useful for basic and translational studies, including in vitro modeling of PD. However, further refinement of methods of induction and maturation of neurons may better recapitulate full development of mDA neurons from hPSCs.
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http://dx.doi.org/10.1038/srep20270 | DOI Listing |
Peptides
January 2025
Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Expression of prokineticin 2 (PK2) mRNA in the suprachiasmatic nucleus (SCN), also knowns as the brain's clock, exhibits circadian oscillations with peak levels midday, zeitgeber time (ZT) 4, and almost undetectable levels during night. This circadian expression profile has substantially contributed to the suggested role of PK2 as an SCN output molecule involved in transmitting circadian rhythm of behavior and physiology. Due to unreliable specificity of PK2 antibodies, the 81 amino acid protein has primarily been studied at the mRNA level and correlation between circadian oscillating mRNAs and protein products are infrequent.
View Article and Find Full Text PDFNeuroscience
December 2024
Departamento de Neurobiología y Neuropatología, IIBCE, MEC, Montevideo, Uruguay. Electronic address:
Iron is one of the crucial elements for CNS development and function and its deficiency (ID) is the most common worldwide nutrient deficit in the world. Iron deficiency anemia (IDA) in pregnant women and infants is a worldwide health problem due to its high prevalence and its irreversible long-lasting effects on brain development. Even with iron supplementation, IDA during pregnancy and/or breastfeeding can result in irreversible cognitive, motor, and behavioral impairments.
View Article and Find Full Text PDFNeuron
December 2024
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene cause Rett syndrome, a severe childhood neurological disorder. MeCP2 is a well-established transcriptional repressor, yet upon its loss, hundreds of genes are dysregulated in both directions. To understand what drives such dysregulation, we deleted Mecp2 in adult mice, circumventing developmental contributions and secondary pathogenesis.
View Article and Find Full Text PDFBMC Ophthalmol
November 2024
Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Objective: The primary objective of this systematic review and meta-analysis was to assess the association between iron deficiency anemia (IDA) and retinal changes via optical coherence tomography (OCT).
Methods: The search was conducted in MEDLINE, Scopus, Embase, Web of Science, and Google Scholar until February 1, 2024. Two independent researchers included the articles based on the inclusion and exclusion criteria.
Epilepsia
November 2024
Saul R. Korey Department of Neurology, Isabelle Rapin Division of Child Neurology, Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.
Early onset epilepsies occur in newborns and infants, and to date, genetic aberrations and variants have been identified in approximately one quarter of all patients. With technological sequencing advances and ongoing research, the genetic diagnostic yield for specific seizure disorders and epilepsies is expected to increase. Genetic variants associated with epilepsy include chromosomal abnormalities and rearrangements of various sizes as well as single gene variants.
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