Memory impairment associated with a dysfunction of the hippocampal cholinergic system induced by prenatal and neonatal exposures to bisphenol-A.
One of the most common chemicals that behaves as an endocrine disruptor is the compound 4,4'-isopronylidenediphenol, called bisphenol-A. In the previous study, we reported that exposure to bisphenol-A induced the abnormality of dopamine receptor functions in the mouse limbic area, resulting in a supersensitivity of drugs of abuse-induced pharmacological actions. The present study was undertaken to investigate whether prenatal and neonatal exposures to bisphenol-A could alter other behavioral abnormalities such as anxiogenic behavior, motor learning behavior, or memory. In the present study, adult female mice were chronically treated with bisphenol-A-admixed powder food from mating to weaning. All experiments were performed using male pups. Here we found that prenatal and neonatal exposures to bisphenol-A failed to induce anxiogenic effects and motor-learning impairment using the light-dark test, elevated plus maze test, and rota-rod test. On the other hand, we found that prenatal and neonatal exposures to bisphenol-A induced the memory impairment using the step-through passive avoidance test. Immunohistochemical study showed the dramatic reduction in choline acetyltransferase-like immunoreactivity, which is a marker of acetylcholine (ACh) production, in the hippocampus of mice prenatally and neonatally exposed to bisphenol-A. These results suggest that chronic exposures to bisphenol-A could induce the memory impairment associated with the reduction in ACh production in the hippocampus.
Miyagawa
Kazuya
K
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawaku, Tokyo 142-8501, Japan.
Narita
Minoru
M
Narita
Michiko
M
Akama
Hisahiko
H
Suzuki
Tsutomu
T
D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001559:Benzhydryl Compounds; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D011930:Reaction Time / Q000187:drug effects; D000098826:Bisphenol A Compounds
D000109:Acetylcholine; D001559:Benzhydryl Compounds; D002795:Choline O-Acetyltransferase; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds