TY - JOUR
T1 - Positive effect of exogenous brain-derived neurotrophic factor on impaired neurite development and mitochondrial function in dopaminergic neurons derived from dental pulp stem cells from children with attention deficit hyperactivity disorder
AU - Nguyen Nguyen, Huong Thi
AU - Kato, Hiroki
AU - Sato, Hiroshi
AU - Yamaza, Haruyoshi
AU - Sakai, Yasunari
AU - Ohga, Shouichi
AU - Nonaka, Kazuaki
AU - Masuda, Keiji
N1 - Funding Information:
We wish to thank all members of the Department of Pediatric and Special Needs Dentistry at Kyushu University Hospital for their valuable suggestions, technical support, and sharing of materials. We appreciate the technical assistance provided by the Research Support Center at the Research Center for Human Disease Modeling , Kyushu University Graduate School of Medical Sciences . This work was supported by the Japan Society for the Promotion of Science (KAKENHI grant numbers JP25670877 , JP16K15839 ).
Funding Information:
We wish to thank all members of the Department of Pediatric and Special Needs Dentistry at Kyushu University Hospital for their valuable suggestions, technical support, and sharing of materials. We appreciate the technical assistance provided by the Research Support Center at the Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences. This work was supported by the Japan Society for the Promotion of Science (KAKENHI grant numbers JP25670877, JP16K15839).
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/6/11
Y1 - 2019/6/11
N2 - Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders and is characterized by impaired attention, hyperactivity, and impulsivity. While multiple etiologies are implicated in ADHD, its underlying mechanism(s) remain unclear. Although previous studies have suggested dysregulation of dopaminergic signals, mitochondria, and brain-derived neurotrophic factor (BDNF) in ADHD, few studies have reported these associations directly. Stem cells from human exfoliated deciduous teeth (SHED) can efficiently differentiate into dopaminergic neurons (DNs) and are thus a useful disease-specific cellular model for the study of neurodevelopmental disorders associated with DN dysfunction. This study aimed to elucidate the relationships between DNs, mitochondria, and BDNF in ADHD by analyzing DNs differentiated from SHED obtained from three boys with ADHD and comparing them to those from three typically developing boys. In the absence of exogenous BDNF in the cell culture media, DNs derived from boys with ADHD (ADHD-DNs) exhibited impaired neurite outgrowth and branching, decreased mitochondrial mass in neurites, and abnormal intracellular ATP levels. In addition, BDNF mRNA was significantly decreased in ADHD-DNs. Supplementation with BDNF, however, significantly improved neurite development and mitochondrial function in ADHD-DNs. These results suggest that ADHD-DNs may have impaired neurite development and mitochondrial function associated with insufficient production of BDNF, which may be improved by exogenous BDNF supplementation. Findings such as these, from patient-derived SHED, may contribute to the future development of treatment strategies for aberrant dopaminergic signaling, mitochondrial functioning, and BDNF levels implicated in ADHD pathogenesis.
AB - Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders and is characterized by impaired attention, hyperactivity, and impulsivity. While multiple etiologies are implicated in ADHD, its underlying mechanism(s) remain unclear. Although previous studies have suggested dysregulation of dopaminergic signals, mitochondria, and brain-derived neurotrophic factor (BDNF) in ADHD, few studies have reported these associations directly. Stem cells from human exfoliated deciduous teeth (SHED) can efficiently differentiate into dopaminergic neurons (DNs) and are thus a useful disease-specific cellular model for the study of neurodevelopmental disorders associated with DN dysfunction. This study aimed to elucidate the relationships between DNs, mitochondria, and BDNF in ADHD by analyzing DNs differentiated from SHED obtained from three boys with ADHD and comparing them to those from three typically developing boys. In the absence of exogenous BDNF in the cell culture media, DNs derived from boys with ADHD (ADHD-DNs) exhibited impaired neurite outgrowth and branching, decreased mitochondrial mass in neurites, and abnormal intracellular ATP levels. In addition, BDNF mRNA was significantly decreased in ADHD-DNs. Supplementation with BDNF, however, significantly improved neurite development and mitochondrial function in ADHD-DNs. These results suggest that ADHD-DNs may have impaired neurite development and mitochondrial function associated with insufficient production of BDNF, which may be improved by exogenous BDNF supplementation. Findings such as these, from patient-derived SHED, may contribute to the future development of treatment strategies for aberrant dopaminergic signaling, mitochondrial functioning, and BDNF levels implicated in ADHD pathogenesis.
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U2 - 10.1016/j.bbrc.2019.04.084
DO - 10.1016/j.bbrc.2019.04.084
M3 - Article
C2 - 31010680
AN - SCOPUS:85064466998
SN - 0006-291X
VL - 513
SP - 1048
EP - 1054
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -
