number of access : ?
number of downloads : ?
ID 109977
Title Alternative
胎生期バルプロ酸曝露によるマウス胚の脊髄神経異常
Spinal nerve defects by prenatal VPA
Author
Bold, Juramt Tokushima University
Keywords
Folic acid
Developmental neurotoxicity
Mice
Spinal nerve
Valproic acid
Content Type
Thesis or Dissertation
Description
To examine in detail spinal nerve defects induced by prenatal exposure to valproic acid in mice, pregnant ICR mice were subcutaneously injected with a single dose of 400 mg/kg valproic acid on gestational day 6, 7, 8, or 9, and their embryos were observed on gestational day 10. The whole-mount immunostaining using an anti-neurofilament antibody allowed us to identify spinal nerve defects, such as a loss of bundle, anastomosis among bundles arising from adjacent segment, and a disrupted segmental pattern of the dorsal root ganglia, in valproic acid-exposed embryos. The prevalence of spinal nerve defects was the highest in the embryos exposed to valproic acid on gestational day8 among the experimental groups. Then, effects of the administration dose of valproic acid on the prevalence of spinal nerve defects were examined on gestational day 10 and found to be dose-dependently increased. It was noteworthy that all embryos exposed to 600 mg/kg of valproic acid on gestational day 8 suffered spinal nerve defects. Folic acid (3 mg/kg/day) supplementation during gestational day 6 to 10 suppressed the prevalence of valproic acid-induced neural tube defects, which are common malformations in offspring prenatally exposed to valproic acid, but not that of spinal nerve defects.Thus, the spinal nerve defects due to prenatal valproic acid exposure might be induced by mechanisms different from those of neural tube defects. Because spinal nerve defects were predicted to be caused by the disrupted segmental arrangement of the somites and/or that of neural crest cells which was the origin of the dorsal root ganglia and/or abnormal polarity of the somite, this mouse model with spinal nerve defects at high incidence, would be useful to examine the effects of valproic acid on somitogenesis and morphogenesis of somite-associated structures.
Journal Title
Anatomical Science International
ISSN
14476959
1447073X
NCID
AA11619036
AA1209993X
Publisher
Springer Japan
Volume
93
Issue
1
Start Page
35
End Page
41
Published Date
2016-08-22
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201611161018.pdf
論文本文 : k2994_fulltext.pdf
本論文は, 著者Juramt Boldの学位論文として提出され, 学位審査・授与の対象となっている。
The final publication is available at Springer via https://doi.org/10.1007/s12565-016-0363-9
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第2994号
Diploma Number
甲医第1299号
Granted Date
2016-09-29
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences