Nov 29, 2019

Single cell analysis of the effects of developmental lead (Pb) exposure on the hippocampus.

bioRxiv
Justin A. ColacinoKelly M. Bakulski

Abstract

Background: Lead (Pb) exposure is ubiquitous and has permanent developmental effects on childhood intelligence and behavior and adulthood risk of dementia. The hippocampus is a key brain region involved in learning and memory, and its cellular composition is highly heterogeneous. Pb acts on the hippocampus by altering gene expression, but the cell type-specific responses are unknown. Objective: Examine the effects of perinatal Pb treatment on adult hippocampus gene expression, at the level of individual cells, in mice. Methods: In mice perinatally exposed to control water (n=4) or a human physiologically-relevant level (32 ppm in maternal drinking water) of Pb (n=4), two weeks prior to mating through weaning, we tested for gene expression and cellular differences in the hippocampus at 5-months of age. Analysis was performed using single cell RNA-sequencing of 5,258 cells from the hippocampus by 10x Genomics Chromium to 1) test for gene expression differences averaged across all cells by treatment; 2) compare cell cluster composition by treatment; and 3) test for gene expression and pathway differences within cell clusters by treatment. Results: Gene expression patterns revealed 12 cell clusters in the hippocampus, mapping to ma...Continue Reading

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Mentioned in this Paper

Study
Biochemical Pathway
Biological Adaptation to Stress
Patterns
toxicant
Sequence Determinations, RNA
Neurons
Brain
Astrocytes
Intelligence

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