Research articleLead exposure in late adolescence through adulthood impairs short-term spatial memory and the neuronal differentiation of adult-born cells in C57BL/6 male mice

- Adult mice were exposed to lead for 12 weeks to model subchronic lead exposure during adolescence and adulthood.
- Subchronic lead exposure during adolescence and adulthood caused persistent deficits in spatial short-term memory.
- Lead-exposed mice had fewer adult-born, mature neurons in the dentate gyrus of the hippocampus compared to controls.

Lead is a neurotoxicant of immense public health importance. Epidemiology studies suggest that heavy metal exposure may be associated with an increased risk of cognitive decline, yet few studies to date have assessed the effect of adult lead exposure on cognitive behavior in animal models. Here, we exposed 6-week-old male C57BL/6 mice to 0.2% lead acetate via drinking water for 12 weeks starting at 6 weeks of age and then assessed for deficits in hippocampus-dependent spatial memory and impairment of adult hippocampal neurogenesis. Lead did not cause locomotor deficits or anxiety in the open field test. However, we found that adult, subchronic lead exposure was sufficient to cause deficits in spatial short-term memory and these deficits persisted through at least 2 months post-lead exposure. Furthermore, we observed that lead-treated mice had fewer adult-born, mature neurons in the dentate gyrus of the hippocampus compared to control animals, suggesting that lead exposure during adolescence and adulthood may impair the neuronal differentiation of adult-born cells. These data suggest that adult lead exposure is sufficient to cause persistent deficits in spatial short-term memory and impair key processes in adult hippocampal neurogenesis.