Sex and rearing condition modify the effects of perinatal lead exposure on learning and memory

Abstract

Developmental lead (Pb) exposure is associated with cognitive impairments in humans and rodents alike. In particular, impaired spatial learning and memory, as assessed using the Morris water maze (MWM), has been noted in developmentally Pb –exposed rats. Although sex and rearing environment can influence MWM performance in normal animals, the interactions of sex and rearing environment on the impact of developmental Pb exposure on hippocampal-dependent processes has not been well characterized. The present study examined the effects of perinatal exposure (i.e., gestation through weaning) to different levels of Pb (250, 750 and 1,500 ppm Pb acetate in food) in males and females raised in a non-enriched environment (standard cage with 3 animals and no toys) or an enriched environment (large cage containing a variety of toys that were changed twice weekly). Testing in the MWM began at postnatal day 55. Behavioral outcomes were influenced by sex and rearing environment, with complex interactions with Pb exposure. In non-Pb exposed control animals, beneficial effects of environmental enrichment on spatial learning and memory were observed in males and females, with greater effects in females. Pb exposure in females mitigated at least some of the benefits of enrichment on learning, particularly at the lowest and highest exposure levels. In males, enrichment conferred a modest learning advantage and for the most part, Pb exposure did not affect this. However, in males with the highest Pb exposure, enrichment did help to overcome detrimental effects of Pb on learning. In females, any potential benefit to reference memory contributed by enrichment was muted by exposure to Pb and for the most part, this was not reproduced in males. Thus, there are complex interactions between sex, environment, and Pb exposure on spatial learning and memory. Environmental manipulation is a potential risk modifier of developmental Pb exposure and interacts with other factors including sex and amount of Pb exposure to affect the functional influences of Pb on the brain.

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

“…We and others have previously reported sex-related differences in hippocampus-based learning and memory (Anderson et al, 2012), gene expression patterns in both the frontal cortex and hippocampus of littermates (Anderson et al, 2013; Schneider et al, 2011) and modulation of epigenetic control elements including DNA methyltransferases of littermates (Schneider et al, 2013) following Pb-exposure. The results of the current study suggest that there are also complex effects of sex, developmental window of exposure and level of Pb-exposure on associative memory as assessed by trace fear conditioning.…”

“…The cognitive/behavioral effects of Pb exposure have been modeled in numerous animal studies, with the majority of studies focusing on hippocampal-associated spatial learning and memory processes in rodents, most often using the Morris water maze (ex., (Jett et al, 1997; Toscano and Guilarte, 2005). Although these studies have provided useful information on the effects of Pb on hippocampus-associated learning and memory, the water maze task may not be optimal for detecting more subtle behavioral disturbances as might occur with lower level exposures to Pb (Anderson et al, 2012; Jett et al, 1997). Other studies have examined the effects of low level developmental Pb exposures (i.e., blood Pb levels < 10μg/dl) on frontal cortex-associated attention and impulsivity problems using fixed-interval/fixed ratio testing or performance on a delay discounting task (Brockel and Cory-Slechta, 1998; Weston et al, 2014).…”

“…We have recently reported significant differences in hippocampus-based spatial learning and memory in males and females following developmental Pb exposure (Anderson et al, 2012). The developmental period during which Pb exposure occurs can also significantly influence cognitive and neurobiological outcomes (Anderson et al, 2012; Schneider et al, 2013).…”

“…The developmental period during which Pb exposure occurs can also significantly influence cognitive and neurobiological outcomes (Anderson et al, 2012; Schneider et al, 2013). Thus, the present study was performed to assess the effects of low level developmental exposure to Pb during different developmental periods on associative learning and memory in males and females, using a trace fear conditioning paradigm.…”

Low-Dose Exposure to Lead during Pregnancy Affects Spatial Learning, Memory and Neurogenesis in Hippocampus of Young Rats

“…The authors concluded that the environmental manipulation was a potential risk modifier of developmental Pb exposure. Furthermore, the authors stated that sex and amount of Pb exposure affected the functional influence of Pb on brain [33]. Thus, results of human and animal studies have reported conflicting results in terms of short-and long-term memory.…”