Altered development of dopaminergic neurons differentiated from stem cells from human exfoliated deciduous teeth of a patient with Down syndrome

Pham, Thanh; Kato, Hiromichi; Yamaza, Haruyoshi; Masuda, Keiji; Satō, Hiroshi; Nguyen, Huyen Thi; Han, Xu; Taguchi, Tomoaki; Nonaka, Kenichi

doi:10.1186/s12883-018-1140-2

Cited by 7 publications

(14 citation statements)

References 35 publications

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“…In this study, SHEDs were obtained from children with DS and were differentiated into DNs in vitro to elucidate the neuropathology of DS. DS‐DNs showed no apparent defects in their differentiation; however, they exhibited impaired neurite development and altered expression of DAT1 and VMAT2 , as previously reported in the analysis of a single case of DS 29 . We also found that DAT1 upregulation via DLK1 downregulation may be implicated in dopamine accumulation and ROS elevation in DS‐DNs.…”

Section: Discussionsupporting

confidence: 84%

“…In the second step, DMEM was replaced by neurobasal medium (Thermo Fisher Scientific) supplemented with 2% B27 supplement (Thermo Fisher Scientific), 1 mM dibutyryladenosine 3,5‐cyclic monophosphate (Nacalai Tesque), 0.5 mM 3‐isobutyl‐1‐methyl‐xanthine (Wako Pure Chemical Industries), and 200 μM ascorbic acid (Nacalai Tesque) (second medium), and cells were incubated for 5 days at 37°C in an incubator with 5% CO 2 . As previously reported, DNs were not fully matured at this stage to allow the strict discrimination between dendrites and axons 29 …”

Section: Methodsmentioning

confidence: 79%

“…SHED isolation and culture were performed as previously described 26–29 . Differentiation from SHEDs to DNs was based on a two‐step procedure described by Fujii et al 24 In the first step, 1.5 × 10 5 SHEDs were plated in a 6‐well culture plate (Corning, NY, USA) and cultured in alpha modification of Eagle's Medium (Nacalai Tesque, Kyoto, Japan) with 15% fetal bovine serum (Sigma‐Aldrich), 100 μM L‐ascorbic acid 2‐phosphate (Wako Pure Chemical Industries), 250 μg/ml fungizone (Thermo Fisher Scientific), 100 U/ml penicillin, and 100 μg/ml streptomycin (Nacalai Tesque).…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies have shown that SHEDs can efficiently differentiate into DNs, making them a potential source of cell‐based therapy for Parkinson's disease with DN degeneration 23–25 . DNs differentiated from patient‐derived SHEDs have also contributed to elucidating dopamine‐related pathologies in several neurodevelopmental disorders 26–30 . Previous analyses using SHEDs from a single case of DS pointed to impaired neurite development, downregulated vesicular monoamine transporter2 ( VMAT2 ) level, and upregulated dopamine transporter1 ( DAT1 ) level in DNs 29 .…”

Section: Introductionmentioning

confidence: 99%

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Dopamine‐related oxidative stress and mitochondrial dysfunction in dopaminergic neurons differentiated from deciduous teeth‐derived stem cells of children with Down syndrome

et al. 2022

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Down syndrome (DS) is one of the common genetic disorders caused by the trisomy of human chromosome 21 (HSA21). Mitochondrial dysfunction and redox imbalance play important roles in DS pathology, and altered dopaminergic regulation has been demonstrated in the brain of individuals with DS. However, the pathological association of these elements is not yet fully understood. In this study, we analyzed dopaminergic neurons (DNs) differentiated from deciduous teeth‐derived stem cells of children with DS or healthy control children. As previously observed in the analysis of a single case of DS, compared to controls, patient‐derived DNs (DS‐DNs) displayed shorter neurite outgrowth and fewer branches, as well as downregulated vesicular monoamine transporter 2 and upregulated dopamine transporter 1, both of which are key regulators of dopamine homeostasis in DNs. In agreement with these expression profiles, DS‐DNs accumulated dopamine intracellularly and had increased levels of cellular and mitochondrial reactive oxygen species (ROS). DS‐DNs showed downregulation of non‐canonical Notch ligand, delta‐like 1, which may contribute to dopamine accumulation and increased ROS levels through DAT1 upregulation. Furthermore, DS‐DNs showed mitochondrial dysfunction in consistent with lower expression of peroxisome proliferator‐activated receptor‐gamma coactivator 1 alpha (PGC‐1α) and upregulation of a HSA21‐encoded negative regulator of PGC‐1α, nuclear receptor‐interacting protein 1. These results suggest that dysregulated dopamine homeostasis may participate in oxidative stress and mitochondrial dysfunction of the dopaminergic system in DS.

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Section: Discussionsupporting

confidence: 84%

Section: Methodsmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dopamine‐related oxidative stress and mitochondrial dysfunction in dopaminergic neurons differentiated from deciduous teeth‐derived stem cells of children with Down syndrome

et al. 2022

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“…They may also experience emotional and behavioral challenges [20][21][22][23], which greatly impact the quality of life of these patients and of the people who care for them. As dopamine (DA) is an important neurotransmitter for cognitive function regulation, it has been pointed out that DA signaling system disturbance causes the cognitive impairments observed in DS [24][25][26][27][28]. DA systems are subject to an accelerator/brake control of their activity [29], which is pivotal for finely shaping DA responses [29,30].…”

Section: Introductionmentioning

confidence: 99%

Down Syndrome in Brazil: Occurrence and Associated Factors

Laignier

Lopes-Júnior

Santana³

et al. 2021

IJERPH

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Background: Down syndrome is the most frequent genetic cause of intellectual disability, with an estimated birth prevalence of 14 per 10,000 live births. In Brazil, statistical data on the occurrence of babies born with Down syndrome remain unclear. We aimed to estimate the occurrence of Down syndrome between 2012 and 2018, and to observe its association with maternal, gestational, paternal characteristics, and newborn vitality. Methods: A retrospective study was carried out using secondary data included in the Certificate of Live Birth in a state located in the southeastern region of Brazil. Data analysis was performed in the software Stata 14.1. Pearson’s chi-square test for bivariate analysis, and logistic regression for multivariate analysis were performed, with a 95% confidence interval (CI) and a significance of 5%. Results: We observed that 157 cases of Down syndrome were reported among 386,571 live births, representing an incidence of 4 in 10,000 live births. Down syndrome was associated with maternal age ≥ 35 years, paternal age ≥ 30 years, the performance of six or more prenatal consultations, prematurity, and low birth weight (p < 0.05). Conclusions: Women aged 35 and over were more likely to have children born with Down syndrome. In addition, there is an association of Down syndrome with premature birth, low birth weight, and the number of prenatal consultations (≥6).

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