title: Developmental exposure to methylmercury alters learning and induces depression-like behavior in male mice.
abstract: To investigate the long-term effects of developmental exposure to methylmercury (MeHg), pregnant mice were exposed to at 0.5 mg MeHg/kg/day via drinking water from gestational day 7 until day 7 after delivery. The behavior of offspring was monitored at 5-15 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.
authors.affiliation: Division of Toxicology and Neurotoxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Natalia
authors.initials: N
authors.lastname: Onishchenko
authors.forename: Christoffer
authors.initials: C
authors.lastname: Tamm
authors.forename: Marie
authors.initials: M
authors.lastname: Vahter
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Johnson
authors.forename: Delinda A
authors.initials: DA
authors.lastname: Johnson
authors.forename: Sandra
authors.initials: S
authors.lastname: Ceccatelli
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003863:Depression / Q000139:chemically induced* / Q000523:psychology*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008628:Mercury / Q000378:metabolism; D020262:Mercury Poisoning, Nervous System / Q000473:pathology / Q000523:psychology*; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011597:Psychomotor Performance / Q000187:drug effects; D020218:Response Elements / Q000502:physiology; D013234:Stem Cells / Q000473:pathology / Q000648:ultrastructure; D013550:Swimming / Q000523:psychology
chemical_list: D000975:Antioxidants; D008767:Methylmercury Compounds; D000469:Alkaline Phosphatase; D008628:Mercury