Early Low-Level Arsenic Exposure Impacts Post-Synaptic Hippocampal Function in Juvenile Mice.

Karl F W Foley,Daniel Barnett,Deborah A Cory-Slechta,Houhui Xia

doi:10.3390/toxics9090206

Karl F W Foley, Daniel Barnett + Show 2 more

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https://doi.org/10.3390/toxics9090206

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Journal: Toxics	Publication Date: Aug 31, 2021
Citations: 5	License type: CC BY 4.0

Affiliation: University of Rochester Medical Center

Abstract

Arsenic is a well-established carcinogen known to increase mortality, but its effects on the central nervous system are less well understood. Epidemiological studies suggest that early life exposure is associated with learning deficits and behavioral changes. Studies in arsenic-exposed rodents have begun to shed light on potential mechanistic underpinnings, including changes in synaptic transmission and plasticity. However, previous studies relied on extended exposure into adulthood, and little is known about the effect of arsenic exposure in early development. Here, we studied the effects of early developmental arsenic exposure in juvenile mice on synaptic transmission and plasticity in the hippocampus. C57BL/6J females were exposed to arsenic (0, 50 ppb, 36 ppm) via drinking water two weeks prior to mating, with continued exposure throughout gestation and parturition. Electrophysiological recordings were then performed on juvenile offspring prior to weaning. In this paradigm, the offspring are exposed to arsenic indirectly, via the mother. We found that high (36 ppm) and relatively low (50 ppb) arsenic exposure both decreased basal synaptic transmission. A compensatory increase in pre-synaptic vesicular release was only observed in the high-exposure group. These results suggest that indirect, ecologically relevant arsenic exposure in early development impacts hippocampal synaptic transmission and plasticity that could underlie learning deficits reported in epidemiological studies.

Highlights

Life exposure to toxic chemicals and environmental pollutants is associated with learning deficits and behavioral changes [1,2,3]
Developmental exposure to low-level arsenic led to an 8% increase in long-term potentiation (LTP) compared to the control (50 ppb: 26% ± 0.06, n = 7), falling between the control and high arsenic exposure, but did not reach statistical significance
Our findings show that early developmental arsenic exposure results in significant changes to hippocampal synaptic transmission and plasticity

Summary

Introduction

Life exposure to toxic chemicals and environmental pollutants is associated with learning deficits and behavioral changes [1,2,3]. An estimated 200 million people worldwide are exposed to arsenic concentrations in drinking water that exceed the World Health Organization’s recommended limit, 10 parts per billion (ppb) [4]. Exposure to concerning levels of arsenic is not limited to toxic waste sites. Arsenic levels commonly exceed 10 ppb in domestic wells throughout the United States, especially in the southwest. While arsenic levels are kept below 10 ppb in municipal water supplies, private wells are unregulated and arsenic levels exceed 10 ppb in 20 out of 37 principal aquifers in the United States [5]. Even mild increases in arsenic exposure are of concern, as exposure is associated with numerous adverse health outcomes and increased mortality from a variety of conditions, including cardiovascular disease and cancer, as well as increased infant mortality [4]. Recent studies suggest the consequences of arsenic exposure can span across generations [6,7,8]

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