Transplacental and early life exposure to inorganic arsenic affected development and behavior in offspring rats

Abstract

To evaluate the developmental neurotoxicity of arsenic in offspring rats by transplacental and early life exposure to sodium arsenite in drinking water, the pregnant rats or lactating dams, and weaned pups were given free access to drinking water, which contained arsenic at concentrations of 0, 10, 50, 100 mg/L from GD 6 until PND 42. A battery of physical and behavioral tests was applied to evaluate the functional outcome of pups. Pups in arsenic exposed groups weighed less than controls throughout lactation and weaning. Body weight of 10, 50 and 100 mg/L arsenic exposed groups decreased significantly on PND 42, 16 and 12, respectively. Physical development (pinna unfolding, fur appearance, incisor eruption, or eye opening) in pups displayed no significant differences between control and arsenic treated groups. The number of incidences within the 100 mg/L arsenic treated group, in tail hung, auditory startle and visual placing showed significant decrease compared to the control group (p < 0.05). In square water maze test, the trained numbers to finish the trials successfully in 50 and 100 mg/L arsenic exposed groups increased remarkably compared to control group, and there was a dose-related increase (p < 0.01) observed. Taken together, these data show that exposure of inorganic arsenite to pregnant dams and offspring pups at levels up to 100 mg/L in drinking water may affect their learning and memory functions and neuromotor reflex.

Cortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMAIII) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression

“…For example, in utero and early life exposure of rodents even to 50 or 100 μg/μL of iAs through drinking water leads to learning and memory deficits in adult offspring [3,13]. In another study, perinatal mice exposure to low iAs concentration (55 μg/L) led to reduced performance in forced swim test and increased response time in learned helplessness [10].…”

“…iAs and its metabolites are eliminated through urine and feces, but an important proportion of them will accumulate in different tissues, including the brain [2]. iAs and its metabolites accumulate in the cerebral cortex, hippocampus, striatum, midbrain, thalamus, pons, medulla oblongata, and pituitary gland of rodents intoxicated with 2.5, 5, and 10 mg/kg/day of sodium arsenite [3,4].…”

Zebrafish as a Model for Developmental Neurotoxicity Assessment: The Application of the Zebrafish in Defining the Effects of Arsenic, Methylmercury, or Lead on Early Neurodevelopment

“…Rodent studies have reported reproducible results showing neurobehavioral and neurophysiological alterations following a developmental arsenic exposure continuing over different periods of time [116][117][118]. In studies conducted under sub-chronic or chronic exposure conditions, rats treated with arsenite from early gestation exhibited behavioral changes with impaired learning/memory ability [117,118].…”

“…In studies conducted under sub-chronic or chronic exposure conditions, rats treated with arsenite from early gestation exhibited behavioral changes with impaired learning/memory ability [117,118]. For instance, rats treated with 36.7 mg/L arsenite from gestation day (GD) 15 through 4 months of age exhibited significant alterations in spontaneous locomotion and poor performance in the delayed alternation test [117].…”

Role of Environmental Chemical Insult in Neuronal Cell Death and Cytoskeleton Damage

“…19,20) Rats and mice exposed to arsenic during gestation and early childhood exhibit behavioral deficits such as changes in locomotor activity, learning, memory, depression-like behavior and neuromotor reflex. [21][22][23] The development of the central nervous system (CNS) in neonatal rats is also affected by arsenic, and exposure to arsenic has been shown to cause neuronal death in the adult rat brain. 24) Sodium arsenite at a concentration of 5 µM induces cytotoxicity at a cellular level via acting as a sulfhydryl reagent, which binds to the free thiol groups of numerous enzymes, inhibiting their functions and depleting levels of glutathione (GSH), thus destroying cell metabolism.…”