Format

Send to

Choose Destination
Biochem Biophys Res Commun. 2019 Jun 11;513(4):1048-1054. doi: 10.1016/j.bbrc.2019.04.084. Epub 2019 Apr 19.

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.

Author information

1
Section of Oral Medicine for Children, Division of Oral Health, Growth & Development, Faculty of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka, 812-8582, Japan.
2
Section of Oral Medicine for Children, Division of Oral Health, Growth & Development, Faculty of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka, 812-8582, Japan. Electronic address: kato@dent.kyushu-u.ac.jp.
3
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka, 812-8582, Japan.
4
Section of Oral Medicine for Children, Division of Oral Health, Growth & Development, Faculty of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka, 812-8582, Japan. Electronic address: kemasuda@dent.kyushu-u.ac.jp.

Abstract

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.

KEYWORDS:

Attention deficit hyperactivity disorder; Brain-derived neurotrophic factor; Dopaminergic neurons; Human exfoliated deciduous teeth stem cells; Mitochondria

PMID:
31010680
DOI:
10.1016/j.bbrc.2019.04.084

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center