Cognitive effects of perinatal exposure to manganese in drinking water, variable stress, and their combination.
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Research indicates that the effects of chemicals may be exacerbated by non-chemical factors such as psychosocial and physical stressors. These stressors, along with many chemicals, are disproportionately found in lower socioeconomic communities and their prevalence has been negatively associated with neurodevelopmental outcomes in children including reduced IQ, memory and attention deficits, and impaired inhibitory control. To understand the cognitive impact of non-chemical stress in combination with exposure to a known neurodevelopmental toxicant, we developed a rodent model of co-occurring perinatal manipulations and conducted a series of cognitive assessments in male and female offspring. Manganese (Mn), a neurodevelopmental toxicant when physiological requirements are exceeded, was delivered in drinking water (0, 2, or 4 mg/mL Mn) of pregnant rats from gestational day (GD) 7 to postnatal day (PND) 22. A variable perinatal stress paradigm was applied to half of the animals from GD13 to PND9. Short term object memory was assessed in adolescent rats using a novel object recognition task. In adults, spatial memory was assessed using the Morris water maze; associative learning and inhibitory control were assessed using autoshaping and differential reinforcement of low-rates procedures; and attention, inhibitory control, and reaction time were assessed using a cued and uncued choice reaction time task. Individually, Mn and stress affected similar cognitive measures including object memory, associative learning, and all choice reaction time measures. These effects were often sex-dependent and task-specific. Given in combination, the changes observed with Mn and stress alone were often attenuated and sex differentiated effects were reduced. Although the dose-response to Mn was altered by stress, this did not lead to greater effects at these Mn concentrations. The results suggest that non-chemical factors can produce long lasting changes in brain function and may play a role in differential susceptibility to chemicals in various populations. This is an abstract of a proposed presentation and does not necessarily reflect US EPA policy.