ArticleBMC neurology2018
Altered development of dopaminergic neurons differentiated from stem cells from human exfoliated deciduous teeth of a patient with Down syndrome.
Article in BMC neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Dopaminergic Perturbation in the Aetiology of Neurodevelopmental Disorders.Molecular neurobiology · 2025Review
- Current insights and prospects for the pathogenesis and treatment of clinical manifestations associated with Down syndrome through neurotransmitter, inflammatory, and oxidative stress pathways.Frontiers in pharmacology · 2025Review
- The Effect of Biomaterials on Human Dental Pulp Stem Cell Neural Differentiation: A Scoping Review.Cell journal · 2023Article
- Analysis and comparisons of gene expression changes in patient- derived neurons from ROHHAD, CCHS, and PWS.Frontiers in pediatrics · 2023Article
- Dopamine-related oxidative stress and mitochondrial dysfunction in dopaminergic neurons differentiated from deciduous teeth-derived stem cells of children with Down syndrome.FASEB bioAdvances · 2022Article
- Down Syndrome in Brazil: Occurrence and Associated Factors.International journal of environmental research and public health · 2021Article
- Challenges and Opportunities for Translation of Therapies to Improve Cognition in Down Syndrome.Trends in molecular medicine · 2020Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDown syndrome (DS) is a common developmental disorder resulting from the presence of an additional copy of chromosome 21. Abnormalities in dopamine signaling are suggested to be involved in cognitive dysfunction, one of the symptoms of DS, but the pathophysiological mechanism has not been fully elucidated at the cellular level. Stem cells from human exfoliated deciduous teeth (SHED) can be prepared from the dental pulp of primary teeth. Importantly, SHED can be collected noninvasively, have multipotency, and differentiate into dopaminergic neurons (DN). Therefore, we examined dopamine signaling in DS at the cellular level by isolating SHED from a patient with DS, differentiating the cells into DN, and examining development and function of DN.
methodsHere, SHED were prepared from a normal participant (Ctrl-SHED) and a patient with DS (DS-SHED). Initial experiments were performed to confirm the morphological, chromosomal, and stem cell characteristics of both SHED populations. Next, Ctrl-SHED and DS-SHED were differentiated into DN and morphological analysis of DN was examined by immunostaining. Functional analysis of DN was performed by measuring extracellular dopamine levels under basal and glutamate-stimulated conditions. In addition, expression of molecules involved in dopamine homeostasis was examined by quantitative real-time polymerase chain reaction and immunostaining. Statistical analysis was performed using two-tailed Student's t-tests.
resultsCompared with Ctrl-SHED, DS-SHED showed decreased expression of nestin, a neural stem-cell marker. Further, DS-SHED differentiated into DN (DS-DN) exhibiting decreased neurite outgrowth and branching compared with Ctrl-DN. In addition, DS-DN dopamine secretion was lower than Ctrl-DN dopamine secretion. Moreover, aberrant expression of molecules involved in dopaminergic homeostasis was observed in DS-DN.
conclusionsOur results suggest that there was developmental abnormality and DN malfunction in the DS-SHED donor in this study. In the future, to clarify the detailed mechanism of dopamine-signal abnormality due to DN developmental and functional abnormalities in DS, it is necessary to increase the number of patients for analysis. Non-invasively harvested SHED may be very useful in the analysis of DS pathology.
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