Low Level Lead Exposure Impairs Attentional Set Shifting Task Performance Depending Upon Sex and Developmental Periods of Exposure

Abstract

Lead (Pb) is a well-known neurotoxin, that when exposed in early development causes lifelong cognitive dysfunction. Pb toxicity research focuses more on memory and motor disturbances and less on executive processes. Further, the extent to which the brain is most susceptible to Pb exposure and its relationship with aberrant cognition remain to be elucidated. Here we examined the effects of an environmentally relevant Pb exposure (150 ppm) in Long Evans Hooded rats abilities to learn simple (SD) and complex (CD) discriminations with reversals (Rev) of compound stimuli (i.e. odors and digging materials presented simultaneously) in the Attention Set Shifting Task (ASST). Rats also learned to cognitively shift within a stimulus dimension (i.e. odor-to-odor) as an Intra-Dimensional Shift (ID) or between stimulus dimensions (i.e. odor-to-material) as an Extra-Dimensional Shift (ED). We examined the differences between gender and three treatment groups: 1) Control (Cont - No Pb Exposure), 2) Perinatal Exposure (Peri- from pairing to birth), and 3) Early Postnatal Exposure (EPN - from birth to parturition). EPN male rats weren't able to learn (CD) and failed to complete the ASST. Peri male rats were able to complete the ASST, but had difficulty with (ID+ID-Rev) when compared to Cont rats, and showed increased latencies to respond during training and in the (ED). Interestingly, EPN female rats were able to complete the ASST and had difficulty in both the (ID+ED-Rev) when compared to Cont rats. Peri female rats completed the ASST with difficulty in the (ED-Rev) when compared to Cont rats. Notably, the Peri female rats performed better than Cont rats on the (ID-Rev). EPN and Peri rats exhibited shorter response latencies in training when compared to Cont rats. In the (ID) stage Peri female rats maintained short latencies to respond while EPN rats were delayed when compared to Cont rats. Results show Pb induced ASST specific deficits on rats cognitive task performance as a function of gender and time of developmental Pb exposure. This suggests that Pb may cause different attention/executive-based cognitive impairments based on the developmental period of exposure due to frontal lobe dysfunction.