Neurobehavioral effects of lead and manganese individually and in combination in developmentally exposed rats. 2012

Swati Betharia, and Timothy J Maher
Massachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USA. sbetharia@manchester.edu

The behavioral effects of exposure to environmentally relevant low levels of the known neurotoxicants lead (Pb) and manganese (Mn) are of current interest, especially when exposure occurs in the period of early development. The incidence of real life neurodevelopmental toxicity is dependent on co-exposure to multiple neurotoxicants present in the environment, and it is therefore important to study these in combination. Pregnant rats were given ad libitum access to drinking water solutions containing Pb (10 μg/mL), Mn (2mg/mL) or a mixture, from beginning of gestation, through lactation and until weaning. Metal-exposed pups were born with significantly higher body weights compared to controls. While female pups exposed to metal mixtures displayed the highest body weights through two months of age, differences were not significant among male pups after the first week. Mixture-exposed pups exhibited the fastest righting times when tested between postnatal days (PNDs) 1 and 10. Learning and memory were assessed in five-day Morris water maze (MWM) tests, ending in probe trials on PNDs 25 and 60. On PND 24, mixture-exposed males performed significantly better than individual metal-exposed males, but this effect was no longer evident between PNDs 56 and 60. Females exposed to Pb or Mn displayed deficits at both behavioral time points. In the open-field test, Mn-exposed males were hypoactive and displayed greater anxiety than controls on PND 24, and showed similar trends when the test was repeated on PND 59. No such differences were observed in female pups or in pups exposed to metal mixture. Metal levels analyzed in blood, brain and milk samples suggested a pharmacokinetic interaction between Pb and Mn. Therefore, developmental exposures to low levels of Pb and Mn can produce gender-specific neurobehavioral deficits, and this study underlines the importance of studying toxicants in combination.

UI MeSH Term Description Entries
D007854 Lead A soft, grayish metal with poisonous salts; atomic number 82, atomic weight 207.2, symbol Pb.
D008297 Male Males
D008345 Manganese A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011297 Prenatal Exposure Delayed Effects The consequences of exposing the FETUS in utero to certain factors, such as NUTRITION PHYSIOLOGICAL PHENOMENA; PHYSIOLOGICAL STRESS; DRUGS; RADIATION; and other physical or chemical factors. These consequences are observed later in the offspring after BIRTH. Delayed Effects, Prenatal Exposure,Late Effects, Prenatal Exposure
D011930 Reaction Time The time from the onset of a stimulus until a response is observed. Response Latency,Response Speed,Response Time,Latency, Response,Reaction Times,Response Latencies,Response Times,Speed, Response,Speeds, Response
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D005106 Exploratory Behavior The tendency to explore or investigate a novel environment. It is considered a motivation not clearly distinguishable from curiosity. Curiosity,Novelty-Seeking Behavior,Behavior, Exploratory,Behavior, Novelty-Seeking,Behaviors, Exploratory,Behaviors, Novelty-Seeking,Curiosities,Exploratory Behaviors,Novelty Seeking Behavior,Novelty-Seeking Behaviors

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