Impairment of learning and memory induced by perinatal exposure to BPA is associated with ERα-mediated alterations of synaptic plasticity and PKC/ERK/CREB signaling pathway in offspring rats

Wu, Dan; Wu, Fengjuan; Lin, Rong; Yuan, Meng; Wei, Wei; Sun, Qi; Jia, Lihong

doi:10.1016/j.brainresbull.2020.04.023

Cited by 39 publications

(38 citation statements)

References 55 publications

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“…The density of dendritic spines changes in response to neural activity; long-term potentiation (LTP) increases spine density [97], whereas long-term depression (LTD) reduces spine density [98]. Chemical exposures can disrupt synaptic plasticity by altering the expression or activity of proteins important for either structural changes in dendritic spines or neuronal signaling pathways that contribute to LTP and LTD. Maternal exposure to BPA has been found to affect the synaptic plasticity of offspring in various brain regions by reducing dendritic spine density [99][100][101], altering LTP and LTD [102,103], and dysregulating the expression of molecular regulators of plasticity (Table 3) [100][101][102][103][104][105][106].…”

Section: Synaptic Plasticity Is Impaired By Bpamentioning

confidence: 99%

“…The impact of BPA on synaptic plasticity in the hippocampus has been extensively investigated because of the key role hippocampal plasticity plays in learning and memory [95]. Reductions in spine density have been observed in the hippocampus of non-human primates [107], rats [99,100,104,105] and mice [106,108] following prenatal or perinatal exposure to BPA at levels ranging from very low dose (30 ug/kg/day) up to high dose (50 mg/kg/day). Analysis of potential molecular causes of reduced hippocampal spine density suggests BPA can downregulate critical synaptic proteins, including presynaptic synapsin I [104,106], postsynaptic density protein 95 (PSD-95) [104-106, 109], N-methyl-D-aspartate (NMDA) receptor subunits [104][105][106]110], α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits [104,105], and activity-regulated cytoskeleton-associated protein (Arc), as well as reduced PKC/ERK/CREB signaling [104].…”

Section: Synaptic Plasticity Is Impaired By Bpamentioning

confidence: 99%

“…Reductions in spine density have been observed in the hippocampus of non-human primates [107], rats [99,100,104,105] and mice [106,108] following prenatal or perinatal exposure to BPA at levels ranging from very low dose (30 ug/kg/day) up to high dose (50 mg/kg/day). Analysis of potential molecular causes of reduced hippocampal spine density suggests BPA can downregulate critical synaptic proteins, including presynaptic synapsin I [104,106], postsynaptic density protein 95 (PSD-95) [104-106, 109], N-methyl-D-aspartate (NMDA) receptor subunits [104][105][106]110], α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits [104,105], and activity-regulated cytoskeleton-associated protein (Arc), as well as reduced PKC/ERK/CREB signaling [104]. While most of these studies exclusively used male animals, two studies that included both sexes reported different impacts in females and males (males were found to have a more robust decrease in spines) [99,104], one study found BPA-associated effects on plasticity were mediated by ER-a [104], while another study suggested plasticity phenotypes were sexindependent because BPA-associated impacts were indistinguishable in male and female brains [100].…”

Section: Synaptic Plasticity Is Impaired By Bpamentioning

confidence: 99%

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Does Bisphenol A Confer Risk of Neurodevelopmental Disorders? What We’ve Learned from Developmental Neurotoxicity Studies in Animal Models

Welch¹,

Mulligan²

2022

Preprint

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Substantial evidence indicates that bisphenol A (BPA), a ubiquitous environmental chemical used in the synthesis of polycarbonate plastics and epoxy resins, can impair brain development. Clinical and epidemiological studies exploring potential connections between BPA and neurodevelopmental disorders in humans have repeatedly identified correlations between early BPA exposure and developmental disorders, like attention deficit/hyperactivity disorder and autism spectrum disorder. Investigations using invertebrate and vertebrate animal models have revealed that developmental exposure to BPA can impair multiple aspects of neuronal development, including neural stem cell proliferation and differentiation, synapse formation, and synaptic plasticity—neuronal phenotypes that are thought to underpin the fundamental changes in behavior associated neurodevelopmental disorders. Consistent with BPA-associated neuronal phenotypes, behavioral analyses of BPA-treated animals have shown significant impacts on behavioral endophenotypes related to neurodevelopmental disorders, including altered locomotor activity, learning and memory deficits, and anxiety-like behavior. To contextualize the correlations between BPA and neurodevelopmental disorders in humans, this review summarizes current literature reporting on the developmental neurotoxicity of BPA in laboratory animals, with an emphasis on neuronal phenotypes, molecular mechanisms, and behavioral outcomes. The collective works described here predominantly support the notion that gestational exposure to BPA should be regarded as a risk factor for neurodevelopmental disorders.

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Section: Synaptic Plasticity Is Impaired By Bpamentioning

confidence: 99%

Section: Synaptic Plasticity Is Impaired By Bpamentioning

confidence: 99%

Section: Synaptic Plasticity Is Impaired By Bpamentioning

confidence: 99%

See 1 more Smart Citation

Does Bisphenol A Confer Risk of Neurodevelopmental Disorders? What We’ve Learned from Developmental Neurotoxicity Studies in Animal Models

Welch¹,

Mulligan²

2022

Preprint

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“…An alarming discovery is the fact that the effects associated with exposure to XEs may manifest in subsequent generations [ 58 , 59 ]. In recent years, XEs exposure has been linked with impaired memory and learning processes, as well as with Attention-Deficit Hyperactivity Disorder in children [ 60 , 61 , 62 ].…”

Section: Xenoestrogens—environmental Estrogensmentioning

confidence: 99%

NF-κB—An Important Player in Xenoestrogen Signaling in Immune Cells

Nowak

Jabłońska

Ratajczak–Wrona

2021

Cells

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The proper functioning of the immune system is critical for an effective defense against pathogenic factors such as bacteria and viruses. All the cellular processes taking place in an organism are strictly regulated by an intracellular network of signaling pathways. In the case of immune cells, the NF-κB pathway is considered the key signaling pathway as it regulates the expression of more than 200 genes. The transcription factor NF-κB is sensitive to exogenous factors, such as xenoestrogens (XEs), which are compounds mimicking the action of endogenous estrogens and are widely distributed in the environment. Moreover, XE-induced modulation of signaling pathways may be crucial for the proper development of the immune system. In this review, we summarize the effects of XEs on the NF-κB signaling pathway. Based on our analysis, we constructed a model of XE-induced signaling in immune cells and found that in most cases XEs activate NF-κB. Our analysis indicated that the indirect impact of XEs on NF-κB in immune cells is related to the modulation of estrogen signaling and other pathways such as MAPK and JAK/STAT. We also summarize the role of these aspects of signaling in the development and further functioning of the immune system in this paper.

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“…EDCs, specifically BPA, could interfere with the endogenous functions of these hormones. In addition, the enzymes involved in xenobiotic biotransformation and the elimination processes of these compounds are not fully developed in the fetus or neonate, thus BPA could persist and accumulate, reaching sufficient levels to cause adverse effects on the target organs in these populations [25,26]. Exposure to BPA early in life could have a transgenerational effect that predisposes later generations to the risk of developing a disease related to this endocrine disruptor.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Indirect Biomarkers of Effect after Exposure to Low Doses of Bisphenol A in a Study of Successive Generations of Mice

Bujalance-Reyes

Molina-López

Ayala-Soldado

et al. 2022

Animals

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Bisphenol A (BPA) is considered as being an emerging pollutant, to which both animal and human populations are continuously and inadvertently exposed. The identification of indirect biomarkers of effect could be a key factor in determining early adverse outcomes from exposure to low doses of BPA. Thus, this study on mice aims to evaluate and identify indirect biomarkers of effect through the analysis of their blood biochemistry, and of certain reproduction parameters after exposure to different BPA concentrations (0.5, 2, 4, 50, and 100 µg/kg BW/day) in drinking water over generations. Our results showed that there were no modifications in the reproductive parameters evaluated, like estrous cycle duration, litter size, or the percentage of the young alive at reaching the weaning stage, at the exposure levels evaluated. However, there were modifications in the biochemical parameters, e.g., alterations in the glucose levels, that increased significantly (p < 0.05) in the breeders at the higher exposure doses (50 and 100 µg/kg BW/day in F1; 50 µg/kg BW/day in F2 and 100 µg/kg BW/day in F3), that would suggest that the BPA could induce hyperglycemia and its complications in adult animals, probably due to some damage in the pancreas cells; albumin, that increased in the breeders exposed to the highest dose in F1 and F3, inferring possible hepatic alterations. Further, total proteins showed a diminution in their values in F1 and F2, except the group exposed to 100 µg/kg BW/day, whereas in F3 the values of this parameter increased with respect to the control group, this aspect likely being related to a possible hepatic and renal alteration. Based on these results, glucose, albumin, and total proteins could initially be considered as early indicators of indirect effect after prolonged exposure to low BPA doses over generations.

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Impairment of learning and memory induced by perinatal exposure to BPA is associated with ERα-mediated alterations of synaptic plasticity and PKC/ERK/CREB signaling pathway in offspring rats

Cited by 39 publications

References 55 publications

Does Bisphenol A Confer Risk of Neurodevelopmental Disorders? What We’ve Learned from Developmental Neurotoxicity Studies in Animal Models

Does Bisphenol A Confer Risk of Neurodevelopmental Disorders? What We’ve Learned from Developmental Neurotoxicity Studies in Animal Models

NF-κB—An Important Player in Xenoestrogen Signaling in Immune Cells

Analysis of Indirect Biomarkers of Effect after Exposure to Low Doses of Bisphenol A in a Study of Successive Generations of Mice

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