Tributyltin Exposure Is Associated With Recognition Memory Impairments, Alterations in Estrogen Receptor α Protein Levels, and Oxidative Stress in the Brain of Female Mice

Abstract

Tributyltin (TBT) is a persistent organometallic pollutant widely used in several agricultural and industrial processes. TBT exposure is associated with various metabolic, reproductive, immune, and cardiovascular abnormalities. However, few studies have evaluated the effects of TBT on behavior. In the present study, we aimed to investigate whether TBT exposure results in oxidative, neuroendocrine, and behavioral alterations. TBT was administered to adult female mice (250, 500, or 750 ng/kg/day or veh for 14 days), and their recognition memory was assessed. We have also evaluated estrogen receptor (ER)α protein expression and oxidative stress (OS) in brain areas related to memory, as well as the correlation between them. A reduction in short- and long-term recognition memory (STM and LTM) performance, as well as in total exploration time was observed in TBT mice. Reduced ERα protein expression was observed in the prefrontal cortex (PFC) and hippocampus of TBT mice, while an increase in TBARS concentration was observed in the PFC of treated animals. Collectively, these data suggest that TBT exposure impairs recognition memory in female mice as a result of, at least in part, its toxicological effects on ERα expression and OS in specific brain areas related to memory.

Marine Pollutant Tributyltin Affects DNA Methylation and Fitness of Banded Murex (Hexaplex trunculus) Populations

“…Despite the significant differences in TBT accumulation and imposex levels between the sites of low and high marine activity, no clear differentiation in snail biomarker responses that could be linked to the impact of TBT (or to the overall marine traffic pollution) was recorded in our study. Previous laboratory exposure experiments indicated that TBT acts as an inducer of oxidative stress in gastropods, fish and mammals [ 70 , 71 , 72 ]. The onset of oxidative stress in native populations of the Buccinanops globulosus gastropod with high imposex occurrence inhabiting harbours has been attributed to TBT and other contaminants such as trace metals and polyaromatic hydrocarbons [ 73 ].…”

p38 and ERK1/2-Dependent Activation of c-Jun Is Required for the Downregulation of Oxidative Stress-Induced ERα in Hypothalamic Astrocytes

“…High glucose-induced oxidative stress alters ERα expression in human endothelial cells [8]. Moreover, tributyltin exposure is associated with recognition memory impairments, alterations in oxidative stress, and ERα protein levels in the brain of female mice [9]; and age-related increase in oxidative stress results in decreased levels of ERα in neuron cells of the cerebral cortex of aging female rats but an increase in the astrocytes [10]. Actually, accumulated evidence had witnessed the role of the oxidative stress on the expression of the estrogen receptor and its consequences on female or male fertility.…”

Environmental Health and Toxicology: Immunomodulation Promoted by Endocrine-Disrupting Chemical Tributyltin

“…Additionally, TBT acts as an inhibitor of aromatase, the enzyme accountable for the conversion of testosterone to estrogen, as well as the estrogen receptor in zebrafish, thereby reducing the effects of ethinylestradiol [ 60 ]. Additionally, numerous studies have revealed that TBT disrupts estrogen signaling, affecting various tissues, as shown in Figure 1 [ 28 , 30 , 33 , 61 , 62 , 63 , 64 , 65 ].…”