Effects of developmental exposure to lead, magnesium and zinc mixtures on spatial learning and expression of NMDA receptor subunit mRNA in Fischer 344 rats.
The N-methyl-D-aspartate receptor (NMDAR) is important for learning. Lead (Pb) exposure impairs learning ability and affects the NMDAR. This study tested whether developmental exposure to a combination of Pb, zinc (Zn), and magnesium (Mg) would result in effects different from those seen with individual metals. Fischer 344 (F344) rat pups of both genders were exposed from gestation day 5 to post-natal day (PND) 40, either to Pb, Mg, or Zn individually or to a (one-third or full concentration) mixture of the three metals. All Zn-treated pups died before PND7, but half of the litters given the full concentration mixture survived to PND40. Impaired learning in the Morris water maze was seen in the Mg and full concentration mixture groups. There were gender differences in NR2A subunit mRNA expression in the hippocampal CA3 region in the Mg and Pb groups, but combining the three metals in the full concentration showed no gender effect. Our results showed that exposure to all three metals affected mortality, learning ability and gender-dependent expression patterns of an NMDAR subunit in a different way from that seen with exposure to the individual metals.
Newman
Heike M
HM
Center for Environmental Toxicology and Technology, Department of Environmental Health, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1676, USA.
Yang
Raymond S H
RS
Magnusson
Kathy R
KR
D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D004338:Drug Combinations; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D007854:Lead / Q000633:toxicity*; D008136:Longevity / Q000187:drug effects; D008274:Magnesium / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D015032:Zinc / Q000633:toxicity*
D004338:Drug Combinations; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D007854:Lead; D008274:Magnesium; D015032:Zinc