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

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.

PP1β opposes classic PP1 function, inhibiting spine maturation and promoting LTP

“…Acute hippocampal slices were prepared from 1-1.5 month-old mice of both sexes as described previously (Foley et al ., 2022; Foley et al, 2021b). After brief isoflurane anesthetization and decapitation, the brain was rapidly dissected and sectioned in an ice-cold high sucrose solution containing, in mM: 215 sucrose, 2.5 KCl, 26 NaHCO 3 , 1.6 NaH 2 PO 4 , 20 D-glucose, 1 CaCl 2 , 4 MgCl 2 , and 4 MgSO 4 .…”

PP1 inhibitor-2 promotes PP1γ positive regulation of synaptic transmission

“…An equivalent number of events was randomly sampled from each I-2 WT cell, yielding 946 events. Acute hippocampal slices were prepared from 1-2-month old mice bred as previously described [30]. 400 μm thick slices were prepared after decapitation and rapid extraction of the brains into ice-cold artificial cerebrospinal fluid (ACSF).…”

Subchronic Arsenic Exposure Induces Behavioral Impairments and Hippocampal Damage in Rats

“…Studies have indicated that arsenic can contribute to nerve damage by inducing an inflammatory response in the hippocampus [ 44 ]. Additionally, arsenic has been found to impact hippocampal autophagy [ 45 ], mitochondrial function [ 46 ], and synaptic function [ 47 ]. As a result, this particular study aimed to investigate the pathological damage inflicted on hippocampal tissue due to arsenic exposure.…”