Lead is a heavy metal of great public health concern in the US and globally. In addition to its well- characterized developmental neurotoxicity, cumulative lead exposure is also neurotoxic to adults and can lead to accelerated, persistent cognitive decline in adult humans. The apolipoprotein E gene (ApoE) exists as three polymorphic alleles in humans (?2, ?3, ?4); the ApoE -?3 allele (simplified as ApoE3 hereafter) is the most common allele. The ApoE-?4 allele (simplified as ApoE4 hereafter) is associated with increased risk for Alzheimer?s disease, and accelerated cognitive decline even in the absence of Alzheimer?s disease pathology. The hippocampus is a region of the brain critical for learning and memory, especially spatial learning. Adult hippocampal neurogenesis is the process whereby adult neural stem cells in the dentate gyrus of the hippocampus leads to the generation and functional integration of adult-born neurons in the hippocampus. These adult-born neurons can influence hippocampus-dependent learning and memory. Although adult neurogenesis is modulated by various extracellular stimuli, by the environment, and by neurotoxicants including lead and ethanol, there is a paucity of information regarding the effect of gene-environment interactions (GxE) on adult neurogenesis. This proposal focuses on the effect of lead-genetic background interactions on adult neurogenesis and hippocampus-dependent learning and memory.
Using lead exposure and APOE-?4 as a useful model, these studies address a critical and timely issue whether there is a GxE on adult hippocampal neurogenesis and on cognitive impairment. These studies may also provide experimental evidence in model organisms that exposure to environmental factors accelerates cognitive decline and neurodegeneration including Alzheimer?s disease through GxE.
|Engstrom, Anna K; Snyder, Jessica M; Maeda, Nobuyo et al. (2017) Correction to: Gene-environment interaction between lead and Apolipoprotein E4 causes cognitive behavior deficits in mice. Mol Neurodegener 12:81|
|Engstrom, Anna K; Xia, Zhengui (2017) Lead exposure in late adolescence through adulthood impairs short-term spatial memory and the neuronal differentiation of adult-born cells in C57BL/6 male mice. Neurosci Lett 661:108-113|
|Engstrom, Anna K; Snyder, Jessica M; Maeda, Nobuyo et al. (2017) Gene-environment interaction between lead and Apolipoprotein E4 causes cognitive behavior deficits in mice. Mol Neurodegener 12:14|