Effects of low level lead exposure on associative learning and memory in the rat: Influences of sex and developmental timing of exposure

Abstract

Lead (Pb) exposure during development impairs a variety of cognitive, behavioral and neurochemical processes resulting in deficits in learning, memory, attention, impulsivity and executive function. Numerous studies have attempted to model this effect of Pb in rodents, with the majority of studies focusing on hippocampus-associated spatial learning and memory processes. Using a different paradigm, trace fear conditioning, a process requiring coordinated integration of both the medial prefrontal cortex and the hippocampus, we have assessed the effects of Pb exposure on associative learning and memory. The present study examined both female and male Long Evans rats exposed to three environmentally relevant levels of Pb (150 ppm, 375 ppm and 750 ppm) during different developmental periods: perinatal (PERI; gestation – postnatal day 21), early postnatal (EPN; postnatal days 1–21) and late postnatal (LPN; postnatal days 1–55). Testing began at postnatal day 55 and consisted of a single day of acquisition training, and three post training time points (1, 2 and 10 days) to assess memory consolidation and recall. All animals, regardless of sex, developmental window or level of Pb-exposure, successfully acquired conditioned-unconditioned stimulus association during training. However, there were significant effects of Pb-exposure on consolidation and memory recall at days 1–10 post training. In females, EPN and LPN exposure to 150 ppm Pb (but not PERI exposure) significantly impaired recall. In contrast, only PERI 150 ppm and 750 ppm-exposed males had significant recall deficits. These data suggest a complex interaction between sex, developmental window of exposure and Pb-exposure level on consolidation and recall of associative memories.

Sexually Dimorphic Effects of Early-Life Exposures to Endocrine Disruptors: Sex-Specific Epigenetic Reprogramming as a Potential Mechanism

“…To more precisely determine the developmental stage when Pb exposure is most important, Anderson et al exposed rats perinatally or postnatally to Pb (0, 150, 375, 750 ppm) and found sex-dependent differences in learning and memory. For example, in a test of memory recall, females were affected more by postnatal exposure to Pb, while males were affected by perinatal exposure [37]. These results may be reflective of the sex-dependent differences in hippocampal transcriptomics this group observed previously [43].…”

“…After a sharp increase in environmental Pb levels at the end of the 20 th century, stringent United States (U.S.) policies were established to limit the use of Pb in gasoline and paint. While these efforts reduced the risk of exposure to both adults and children [37], early-life exposure to Pb remains a major public health concern. The U.S. Centers for Disease Control and Prevention (CDC) estimates there to be at least 4 million US households where children are exposed to high levels of Pb, primarily through the ingestion of paint [38].…”

Sex- and brain region- specific effects of prenatal stress and lead exposure on permissive and repressive post-translational histone modifications from embryonic development through adulthood

“…Adverse neurodevelopmental effects of Pb, PS and the combination, as demonstrated in human studies and paralleled in animal models, can be persistent (Anderson et al, 2016; Brubaker et al, 2010; Canfield et al, 2003; Cecil et al, 2008; Cohn et al, 1993; Jett et al, 1997; Lanphear et al, 2005; Li et al, 2016). Findings from this study confirm long-lasting changes in PTHM levels in response to these exposures, as evidenced in FC and HIPP at PND60 with Pb exposure having been discontinued at PND21, with effects differing by sex and by brain region.…”

Strain specific effects of low level lead exposure on associative learning and memory in rats

“…All experimental animals were generated in house to reduce outside sources of potential variability. In the PERI exposure group, 50–55 day old LE dams (Envigo Laboratories) and SD dams (Taconic Laboratories) were fed chow (RMH 1000) with or without added Pb acetate (150 ppm or 0 ppm) for 14 days prior to breeding and remained on the same diet through weaning, as previously described (Anderson et al, 2016). Thus, dams were continuously exposed to Pb for approximately 55–60 days.…”