PMID- 18485098
OWN - NLM
STAT- MEDLINE
DCOM- 20080915
LR  - 20220314
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 106
IP  - 3
DP  - 2008 Aug
TI  - Long-lasting depression-like behavior and epigenetic changes of BDNF gene 
      expression induced by perinatal exposure to methylmercury.
PG  - 1378-87
LID - 10.1111/j.1471-4159.2008.05484.x [doi]
AB  - Substantial evidence indicates that predisposition to diseases can be acquired 
      during early stages of development and interactions between environmental and 
      genetic factors may be implicated in the onset of many pathological conditions. 
      Data collected over several decades have shown that chemicals are among the 
      relevant factors that can endanger CNS. We previously showed that perinatal 
      exposure to methylmercury (MeHg) causes persistent changes in learning and 
      motivational behavior in mice. In this study, we report that the depression-like 
      behavior in MeHg-exposed male mice is reversed by chronic treatment with the 
      antidepressant fluoxetine. Behavioral alterations are associated with a decrease 
      in brain-derived neurotrophic factor (BDNF) mRNA in the hippocampal dentate gyrus 
      and fluoxetine treatment restores BDNF mRNA expression. We also show that 
      MeHg-exposure induces long-lasting repressive state of the chromatin structure at 
      the BDNF promoter region, in particular DNA hypermethylation, an increase in 
      histone H3-K27 tri-methylation and a decrease in H3 acetylation at the promoter 
      IV. While fluoxetine treatment does not alter hypermethylation of H3-K27, it 
      significantly up-regulates H3 acetylation at the BDNF promoter IV in MeHg-exposed 
      mice. Our study shows that developmental exposure to low levels of MeHg 
      predisposes mice to depression and induces epigenetic suppression of BDNF gene 
      expression in the hippocampus.
FAU - Onishchenko, Natalia
AU  - Onishchenko N
AD  - Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
FAU - Karpova, Nina
AU  - Karpova N
FAU - Sabri, Farideh
AU  - Sabri F
FAU - Castren, Eero
AU  - Castren E
FAU - Ceccatelli, Sandra
AU  - Ceccatelli S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080515
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Methylmercury Compounds)
RN  - 01K63SUP8D (Fluoxetine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/*genetics
MH  - Depression/chemically induced/drug therapy/*metabolism
MH  - Epigenesis, Genetic/*drug effects/physiology
MH  - Female
MH  - Fluoxetine/therapeutic use
MH  - Gene Expression Regulation, Developmental/*drug effects/physiology
MH  - Immobilization
MH  - Male
MH  - Methylmercury Compounds/*toxicity
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/genetics/*metabolism
EDAT- 2008/05/20 09:00
MHDA- 2008/09/16 09:00
CRDT- 2008/05/20 09:00
PHST- 2008/05/20 09:00 [pubmed]
PHST- 2008/09/16 09:00 [medline]
PHST- 2008/05/20 09:00 [entrez]
AID - JNC5484 [pii]
AID - 10.1111/j.1471-4159.2008.05484.x [doi]
PST - ppublish
SO  - J Neurochem. 2008 Aug;106(3):1378-87. doi: 10.1111/j.1471-4159.2008.05484.x. Epub 
      2008 May 15.