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

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...

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Main Authors: Karl F. W. Foley, Daniel Barnett, Deborah A. Cory-Slechta, Houhui Xia
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Toxics
Subjects:
Online Access:https://www.mdpi.com/2305-6304/9/9/206
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spelling doaj-835d00eb487446a780c0f2be6a7939622021-09-26T01:33:13ZengMDPI AGToxics2305-63042021-08-01920620610.3390/toxics9090206Early Low-Level Arsenic Exposure Impacts Post-Synaptic Hippocampal Function in Juvenile MiceKarl F. W. Foley0Daniel Barnett1Deborah A. Cory-Slechta2Houhui Xia3Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Pharmacology & Physiology, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, USAArsenic 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.https://www.mdpi.com/2305-6304/9/9/206arsenicsynaptic transmissionlong-term potentiationhippocampusdevelopment
collection DOAJ
language English
format Article
sources DOAJ
author Karl F. W. Foley
Daniel Barnett
Deborah A. Cory-Slechta
Houhui Xia
spellingShingle Karl F. W. Foley
Daniel Barnett
Deborah A. Cory-Slechta
Houhui Xia
Early Low-Level Arsenic Exposure Impacts Post-Synaptic Hippocampal Function in Juvenile Mice
Toxics
arsenic
synaptic transmission
long-term potentiation
hippocampus
development
author_facet Karl F. W. Foley
Daniel Barnett
Deborah A. Cory-Slechta
Houhui Xia
author_sort Karl F. W. Foley
title Early Low-Level Arsenic Exposure Impacts Post-Synaptic Hippocampal Function in Juvenile Mice
title_short Early Low-Level Arsenic Exposure Impacts Post-Synaptic Hippocampal Function in Juvenile Mice
title_full Early Low-Level Arsenic Exposure Impacts Post-Synaptic Hippocampal Function in Juvenile Mice
title_fullStr Early Low-Level Arsenic Exposure Impacts Post-Synaptic Hippocampal Function in Juvenile Mice
title_full_unstemmed Early Low-Level Arsenic Exposure Impacts Post-Synaptic Hippocampal Function in Juvenile Mice
title_sort early low-level arsenic exposure impacts post-synaptic hippocampal function in juvenile mice
publisher MDPI AG
series Toxics
issn 2305-6304
publishDate 2021-08-01
description 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.
topic arsenic
synaptic transmission
long-term potentiation
hippocampus
development
url https://www.mdpi.com/2305-6304/9/9/206
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