PMID- 19460635
OWN - NLM
STAT- MEDLINE
DCOM- 20090723
LR  - 20200106
IS  - 1873-474X (Electronic)
IS  - 0736-5748 (Linking)
VI  - 27
IP  - 4
DP  - 2009 Jun
TI  - Observation of fetal brain in a rat valproate-induced autism model: a 
      developmental neurotoxicity study.
PG  - 399-405
LID - 10.1016/j.ijdevneu.2009.01.006 [doi]
AB  - Prenatal exposure to chemicals is well known to induce developmental 
      abnormalities in the central nervous system of children. Developmental 
      neurotoxicity (DNT) tests are important to identify neurotoxic agents and prevent 
      neurodevelopmental disorders. We have investigated DNT, focusing on the fetal 
      brain shortly after chemical exposure. To demonstrate a usefulness of a study 
      focusing on the fetal brain in DNT tests, we assessed the fetal brain in a rat 
      valproate-induced autism model. Rats were treated with sodium valproate (VPA, 800 
      mg/kg) orally on gestational day (GD) 9 or 11 (VPA9 or VPA11), and the fetal 
      brains were examined on GD16 using immunohistochemistry for serotonin (5-HT), 
      tyrosine hydroxylase (TH), and TuJ1 (neuron specific class III beta-tubulin). 
      Hypoplasia of the cortical plate was induced in both VPA9 and VPA11 groups. 
      Abnormal migration of TH-positive and 5-HT neurons, possibly due to the 
      appearance of an abnormally running nerve tract in the pons, was observed only in 
      the VPA11 group. In addition, when we compared the incidence of these 
      abnormalities between pregnant rats mated in our own animal facility (in-house 
      group), and rats purchased pregnant (supplier group), the supplier group was much 
      more sensitive, especially to the pons abnormality. Shipping stress may affect 
      the reproducibility of VPA-induced DNT. The present results demonstrate that 
      examination of the GD16 fetal brain was useful for detecting and characterizing 
      abnormal development of the brain after VPA exposure. Further discussion was made 
      with reference to the findings in children with autism.
FAU - Kuwagata, Makiko
AU  - Kuwagata M
AD  - Laboratory of Pathology, Division of Toxicology, Hatano Research Institute, Food 
      and Drug Safety Center, Kanagawa, Japan. kuwagata.m@fdsc.or.jp
FAU - Ogawa, Tetsuo
AU  - Ogawa T
FAU - Shioda, Seiji
AU  - Shioda S
FAU - Nagata, Tomoko
AU  - Nagata T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090129
PL  - United States
TA  - Int J Dev Neurosci
JT  - International journal of developmental neuroscience : the official journal of the 
      International Society for Developmental Neuroscience
JID - 8401784
RN  - 0 (Anticonvulsants)
RN  - 614OI1Z5WI (Valproic Acid)
SB  - IM
MH  - Animals
MH  - Anticonvulsants/*pharmacology
MH  - *Autistic Disorder/chemically induced/physiopathology
MH  - *Brain/anatomy & histology/drug effects/pathology
MH  - Disease Models, Animal
MH  - Female
MH  - *Fetus/drug effects/physiology
MH  - Humans
MH  - Male
MH  - Neurotoxicity Syndromes/etiology/physiopathology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/chemically induced
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Valproic Acid/*pharmacology
EDAT- 2009/05/23 09:00
MHDA- 2009/07/25 09:00
CRDT- 2009/05/23 09:00
PHST- 2008/11/09 00:00 [received]
PHST- 2009/01/16 00:00 [revised]
PHST- 2009/01/22 00:00 [accepted]
PHST- 2009/05/23 09:00 [entrez]
PHST- 2009/05/23 09:00 [pubmed]
PHST- 2009/07/25 09:00 [medline]
AID - S0736-5748(09)00018-5 [pii]
AID - 10.1016/j.ijdevneu.2009.01.006 [doi]
PST - ppublish
SO  - Int J Dev Neurosci. 2009 Jun;27(4):399-405. doi: 10.1016/j.ijdevneu.2009.01.006. 
      Epub 2009 Jan 29.