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

Abstract

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.

Down syndrome child with multiple heart diseases: A case report

“…The assessment process involves echocardiography to determine the morphological changes in the heart and detect the presence of PH. Generally, evaluation of pulmonary arterial compression is conducted using the three-pointed reflux peak speed and Doppler ultrasonic images in combination with other ultrasonic indicators that could potentially indicate PH, such as increased pulmonary valve reflux speed, enlargement of the right heart cavity, and enlargement of the main pulmonary artery[ 20 ]. Evaluation also includes clinical manifestations, peripheral blood oxygen saturation, and other indicators to determine the level of PH.…”

Mitochondrial Calcium-Triggered Oxidative Stress and Developmental Defects in Dopaminergic Neurons Differentiated from Deciduous Teeth-Derived Dental Pulp Stem Cells with MFF Insufficiency

“…Analyses of neuronal morphology and mitochondrial volume in the DNs were performed as previously described [ 33 ]. To measure the maximum neurite length and the total number of neurite branches, TH- and DAPI-stained pictures were acquired and 30 cells of each case were analyzed with the Neurite Outgrowth module in MetaMorph software version 7.8 (Molecular Devices, San Jose, CA, USA).…”

“…Total RNA extraction and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were performed as previously described [ 33 ]. The sequence information of the primer sets that are used in this study are listed in Table 1 .…”

“…Mitochondrial reactive oxygen species (ROS) levels were determined using flow cytometry and confocal microscopy, as previously described [ 33 ]. To determine mitochondrial ROS levels using flow cytometry, the cells were incubated with 5 µM of MitoSOX Red (Thermo Fisher Scientific) for 30 min.…”

“…Intracellular adenosine triphosphate (ATP) levels were measured, as previously described [ 33 ]. The cells were harvested in ice-cold PBS, and the CellTiter-Glo Luminescent Cell Viability Assay (Promega, Fitchburg, WI, USA) was then used to measure the intracellular ATP levels.…”