Aromatic L-amino Acid Decarboxylase (AADC) is Crucial for Brain Development and Motor Functions
Date Issued
2016
Date
2016
Author(s)
Shih, De-Fen
Abstract
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare pediatric neuro-metabolic disease in children. Due to the lack of an animal model, its pathogenetic mechanism is poorly understood. To study the role of AADC in brain development, a zebrafish model of AADC deficiency was generated. Whole-mount in situ hybridization analysis showed that the aadc gene was specifically expressed in the epiphysis, locus coeruleus, dipencephalic catecholaminergic (DC) clusters, and raphe nuclei of 36-h post-fertilization (hpf) zebrafish embryos. Inhibition of AADC by the inhibitor NSD-1015 or anti-sense morpholino (MO) led to a reduction brain volume and body length. There was an increased apoptosis occurrence in the brain and a loss of DC cluster neurons in AADC morphants (aadc MO-injected embryos). Seizure-like activity was also detected in AADC morphants in a dose-dependent manner. The AADC morphants were less sensitive in touch response and had a reduced swimming activity, and these phenotypes were rescued by injection of aadc plasmids. In conclusion, inhibition of AADC may reduce brain size, increase apoptosis, and reduce motor function in zebrafish. Zebrafish can be a useful model for investigating the pathogenetic mechanisms of AADC deficiency in children.
Subjects
AADC deficiency
dopamine
zebrafish
morpholino
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-105-D96B41007-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):3ae50b057f2a6581a09734528e1254bc