PMID- 23220560
OWN - NLM
STAT- MEDLINE
DCOM- 20130408
LR  - 20130222
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 304
DP  - 2013 Feb 8
TI  - Low level prenatal exposure to methylmercury disrupts neuronal migration in the 
      developing rat cerebral cortex.
PG  - 57-68
LID - S0300-483X(12)00416-7 [pii]
LID - 10.1016/j.tox.2012.11.019 [doi]
AB  - We determined the effects of low-level prenatal MeHg exposure on neuronal 
      migration in the developing rat cerebral cortex using in utero electroporation. 
      We used offspring rats born to dams that had been exposed to saline or various 
      doses of MeHg (0.01 mg/kg/day, 0.1 mg/kg/day, and 1 mg/kg/day) from gestational 
      day (GD) 11-21. Immunohistochemical examination of the brains of the offspring 
      was conducted on postnatal day (PND) 0, PND3, and PND7. Our results showed that 
      prenatal exposure to low levels of MeHg (0.1 mg/kg/day or 1 mg/kg/day) during the 
      critical stage in neuronal migration resulted in migration defects of the 
      cerebrocortical neurons in offspring rats. Importantly, our data revealed that 
      the abnormal neuronal distribution induced by MeHg was not caused by altered 
      proliferation of neural progenitor cells (NPCs), induction of apoptosis of NPCs 
      and/or newborn neurons, abnormal differentiation of NPCs, and the morphological 
      changes of radial glial scaffold, indicating that the defective neuronal 
      positioning triggered by exposure to low-dose of MeHg is due to the impacts of 
      MeHg on the process of neuronal migration itself. Moreover, we demonstrated that 
      in utero exposure to low-level MeHg suppresses the expression of Rac1, Cdc42, and 
      RhoA, which play key roles in the migration of cerebrocortical neurons during the 
      early stage of brain development, suggesting that the MeHg-induced migratory 
      disturbance of cerebrocortical neurons is likely associated with the Rho GTPases 
      signal pathway. In conclusion, our results provide a novel perspective on 
      clarifying the mechanisms underlying the impairment of neuronal migration induced 
      by MeHg.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Guo, Bao-Qiang
AU  - Guo BQ
AD  - MOE-Shanghai Key Laboratory of Children's Environmental Health, XinHua Hospital 
      affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, 
      China.
FAU - Yan, Chong-Huai
AU  - Yan CH
FAU - Cai, Shi-Zhong
AU  - Cai SZ
FAU - Yuan, Xiao-Bing
AU  - Yuan XB
FAU - Shen, Xiao-Ming
AU  - Shen XM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121207
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Methylmercury Compounds)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
RN  - RWZ4L3O1X0 (methylmercuric chloride)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/drug effects
MH  - Cell Differentiation/drug effects
MH  - Cell Movement/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Cerebral Cortex/*drug effects/metabolism/pathology
MH  - Dose-Response Relationship, Drug
MH  - Electroporation
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Maternal Exposure
MH  - Methylmercury Compounds/administration & dosage/*toxicity
MH  - Neurons/*drug effects/pathology
MH  - Pregnancy
MH  - Rats
MH  - Signal Transduction/drug effects
MH  - Time Factors
MH  - cdc42 GTP-Binding Protein/genetics
MH  - rac1 GTP-Binding Protein/genetics
MH  - rho GTP-Binding Proteins/metabolism
MH  - rhoA GTP-Binding Protein/genetics
EDAT- 2012/12/12 06:00
MHDA- 2013/04/09 06:00
CRDT- 2012/12/11 06:00
PHST- 2012/09/20 00:00 [received]
PHST- 2012/11/11 00:00 [revised]
PHST- 2012/11/15 00:00 [accepted]
PHST- 2012/12/11 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2013/04/09 06:00 [medline]
AID - S0300-483X(12)00416-7 [pii]
AID - 10.1016/j.tox.2012.11.019 [doi]
PST - ppublish
SO  - Toxicology. 2013 Feb 8;304:57-68. doi: 10.1016/j.tox.2012.11.019. Epub 2012 Dec 
      7.