Developmental exposure to methylmercury alters learning and induces depression-like behavior in male mice

被引:129
作者
Onishchenko, Natalia
Tamm, Christoffer
Vahter, Marie
Hokfelt, Tomas
Johnson, Jeffrey A.
Johnson, Delinda A.
Ceccatelli, Sandra
机构
[1] Karolinska Inst, Inst Environm Med, Div Toxicol & Neurosci, S-17177 Stockholm, Sweden
[2] Karolinska Inst, Inst Environm Med, Div Met & Hlth, S-17177 Stockholm, Sweden
[3] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden
[4] Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA
关键词
developmental neurotoxicity; behavior; neural stem cells;
D O I
10.1093/toxsci/kfl199
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
To investigate the long-term effects of developmental exposure to methylmercury (MeHg), pregnant mice were exposed to at 0.5 mg MeHg/kglday via drinking water from gestational day 7 until day 7 after delivery. The behavior of offspring was monitored at 515 and 26-36 weeks of age using an automated system (IntelliCage) designed for continuous long-term recording of the home cage behavior in social groups and complex analysis of basic activities and learning. In addition, spontaneous locomotion, motor coordination on the accelerating rotarod, spatial learning in Morris water maze, and depression-like behavior in forced swimming test were also studied. The analysis of behavior performed in the IntelliCage without social deprivation occurred to be more sensitive in detecting alterations in activity and learning paradigms. We found normal motor function but decreased exploratory activity in MeHg-exposed male mice, especially at young age. Learning disturbances observed in MeHg-exposed male animals suggest reference memory impairment. Interestingly, the forced swimming test revealed a predisposition to depressive-like behavior in the MeHg-exposed male offspring. This study provides novel evidence that the developmental exposure to MeHg can affect not only cognitive functions but also motivation-driven behaviors.
引用
收藏
页码:428 / 437
页数:10
相关论文
共 52 条
[1]   PRENATAL METHYLMERCURY POISONING - CLINICAL OBSERVATIONS OVER 5 YEARS [J].
AMINZAKI, L ;
MAJEED, MA ;
ELHASSANI, SB ;
CLARKSON, TW ;
GREENWOOD, MR ;
DOHERTY, RA .
AMERICAN JOURNAL OF DISEASES OF CHILDREN, 1979, 133 (02) :172-177
[2]  
[Anonymous], 2000, TOX EFF METH MERC
[3]  
[Anonymous], 1986, 3080 NAT SWED ENV BO
[4]   EFFECT OF METHYLMERCURY CHLORIDE ON SLEEP-WAKING RHYTHMS IN RATS [J].
ARITO, H ;
HARA, N ;
TORII, S .
TOXICOLOGY, 1983, 28 (04) :335-345
[5]   Acquisition of dominance status affects maze learning in mice [J].
Barnard, CJ ;
Luo, N .
BEHAVIOURAL PROCESSES, 2002, 60 (01) :53-59
[6]   METHYLMERCURY DEVELOPMENTAL NEUROTOXICITY - A COMPARISON OF EFFECTS IN HUMANS AND ANIMALS [J].
BURBACHER, TM ;
RODIER, PM ;
WEISS, B .
NEUROTOXICOLOGY AND TERATOLOGY, 1990, 12 (03) :191-202
[7]   EVIDENCE THAT EXPOSURE TO METHYL MERCURY DURING GESTATION INDUCES BEHAVIORAL AND NEUROCHEMICAL CHANGES IN OFFSPRING OF RATS [J].
CAGIANO, R ;
DESALVIA, MA ;
RENNA, G ;
TORTELLA, E ;
BRAGHIROLI, D ;
PARENTI, C ;
ZANOLI, P ;
BARALDI, M ;
ANNAU, Z ;
CUOMO, V .
NEUROTOXICOLOGY AND TERATOLOGY, 1990, 12 (01) :23-28
[8]   Acute exposure to methylmercury at two developmental windows:: Focus on neurobehavioral and neurochemical effects in rat offspring [J].
Carratu, M. R. ;
Borracci, P. ;
Coluccia, A. ;
Giustino, A. ;
Renna, G. ;
Tomasini, M. C. ;
Raisi, E. ;
Antonelli, T. ;
Cuomo, V. ;
Mazzoni, E. ;
Ferraro, L. .
NEUROSCIENCE, 2006, 141 (03) :1619-1629
[9]   Neurotoxicity and molecular effects of methylmercury [J].
Castoldi, AF ;
Coccini, T ;
Ceccatelli, S ;
Manzo, L .
BRAIN RESEARCH BULLETIN, 2001, 55 (02) :197-203
[10]  
Daré E, 2000, J NEUROSCI RES, V62, P557, DOI 10.1002/1097-4547(20001115)62:4<557::AID-JNR10>3.0.CO