Suppressive Effects of Bisphenol A on the Proliferation of Neural Progenitor Cells

Kim, Keun-Ho; Son, Tae Gen; Kim, So Jung; Kim, Hyung Sik; Kim, Tae Sung; Han, Soon Young; Lee, Joo Young

doi:10.1080/15287390701434216

Cited by 59 publications

(40 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Bisphenol A (BPA), is an endocrinedisrupting synthetic xenoestrogen, widely distributed in the environment, and used for the production of number of polycarbonate plastics and epoxy resin-containing consumer products [16,17]. BPA leaches out from the consumer products and upon ingestion crosses the placental and blood-brain barrier, leading to injury to the developing and adult brain [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway

et al. 2015

View full text Add to dashboard Cite

Bisphenol A (BPA) is an environmental xenoestrogenic endocrine disruptor, utilized for production of consumer products, and exerts adverse effects on the developing nervous system. Recently, we found that BPA impairs the finely tuned dynamic processes of neurogenesis (generation of new neurons) in the hippocampus of the developing rat brain. Curcumin is a natural polyphenolic compound, which provides neuroprotection against various environmental neurotoxicants and in the cellular and animal models of neurodegenerative disorders. Here, we have assessed the neuroprotective efficacy of curcumin against BPA-mediated reduced neurogenesis and the underlying cellular and molecular mechanism(s). Both in vitro and in vivo studies showed that curcumin protects against BPA-induced hippocampal neurotoxicity. Curcumin protects against BPA-mediated reduced neural stem cells (NSC) proliferation and neuronal differentiation and enhanced neurodegeneration. Curcumin also enhances the expression/levels of neurogenic and the Wnt pathway genes/proteins, which were reduced due to BPA exposure in the hippocampus. Curcumin-mediated neuroprotection against BPA-induced neurotoxicity involved activation of the Wnt/β-catenin signaling pathway, which was confirmed by the use of Wnt specific activators (LiCl and GSK-3β siRNA) and inhibitor (Dkk-1). BPA-mediated increased β-catenin phosphorylation, decreased GSK-3β levels, and β-catenin nuclear translocation were significantly reversed by curcumin, leading to enhanced neurogenesis. Curcumin-induced protective effects on neurogenesis were blocked by Dkk-1 in NSC culture treated with BPA. Curcumin-mediated enhanced neurogenesis was correlated well with improved learning and memory in BPA-treated rats. Overall, our results conclude that curcumin provides neuroprotection against BPA-mediated impaired neurogenesis via activation of the Wnt/β-catenin signaling pathway.

show abstract

Section: Introductionmentioning

confidence: 99%

Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In some studies, cell proliferation was unaffected by any concentration of BPA that was tested (for example (Dominguez et al, 2008)). In other studies, only monotonic responses were reported for cell proliferation (for example (Kim et al, 2007;Kochukov et al, 2009;Okada et al, 2008;Park et al, 2009)). Finally, still other studies reported non-monotonic responses for cell proliferation (for example (Bouskine et al, 2009;Ricupito et al, 2009;Sheng and Zhu, 2011;Wu et al, 2012)).…”

Section: Nmdrcs Occur For Many Different Endpointsmentioning

confidence: 99%

Non-Monotonic Dose Responses in Studies of Endocrine Disrupting Chemicals: Bisphenol a as a Case Study

Vandenberg¹

2013

Dose-Response

283

152

View full text Add to dashboard Cite

ᮀ Non-monotonic dose response curves (NMDRCs) have been demonstrated for natural hormones and endocrine disrupting chemicals (EDCs) in a variety of biological systems including cultured cells, whole organ cultures, laboratory animals and human populations. The mechanisms responsible for these NMDRCs are well known, typically related to the interactions between the ligand (hormone or EDC) and a hormone receptor. Although there are hundreds of examples of NMDRCs in the EDC literature, there are claims that they are not 'common enough' to influence the use of high-to-low dose extrapolations in risk assessments. Here, we chose bisphenol A (BPA), a well-studied EDC, to assess the frequency of non-monotonic responses. Our results indicate that NMDRCs are common in the BPA literature, occurring in greater than 20% of all experiments and in at least one endpoint in more than 30% of all studies we examined. We also analyzed the types of endpoints that produce NMDRCs in vitro and factors related to study design that influence the ability to detect these kinds of responses. Taken together, these results provide strong evidence for NMDRCs in the EDC literature, specifically for BPA, and question the current risk assessment practice where 'safe' low doses are predicted from high dose exposures.

show abstract

“…Moreover, a large amount of data has shown that BPA may not only change physiological processes in adults, but also could be destructive and cause alterations in nervous system development with accompanying morphological changes. In vitro, BPA significantly impairs the proliferation of neural progenitor cells and at high-doses it is even cytotoxic to them [10].…”

Section: Introductionmentioning

confidence: 99%

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

Thoene

Godlewski

Rytel

et al. 2018

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Introduction. Bisphenol A (BPA) is used in the chemical industry for manufacturing plastics which are used as food packaging. Data indicate that BPA is released from such products and is widely present in the environment and the human body. So far, the EFSA and the US FDA have determined "safe" BPA oral exposure levels, and a large amount of data indicates that BPA is harmful even at low-doses. Our previously performed analyses concerning BPA exposure demonstrated the impact of this substance on parasympathetic and peptidergic nerve fibers present within the liver. Therefore, this study concerns BPA exposure and sympathetic intrahepatic innervation in reference to several neuropeptides which modulate neuronal responses: cocaine and amphetamine regulated transcript (CART), galanin (GAL), calcitonin gene-regulated peptide (CGRP) and substance P (SP). Materials and methods. Fifteen young swine at 8 weeks of age were used as experimental models of the juvenile human liver. The pigs were divided into 3 groups and received capsules orally with bisphenol at a dose of 0.05 mg/kg b.w./day; a dose of 0.5 mg/kg b.w./day and placebo capsules as a control. After 28 days of oral BPA intake, the animals were euthanized, perfused with 4% paraformaldehyde (PFA), and livers were collected and fixed in PFA. The cryostat sections were subjected to a routine double-labeling immunofluorescence technique. The primary antibodies were directed against dopamine beta hydroxylase (DbH), which is a marker for sympathetic nerves, and one of the investigated neuropeptides: CART, GAL, CGRP and SP, which co-localized the investigated nerves. Immunoreactive nerves were counted in the liver and the percentage presence of each neuronal combination in particular samples of each experimental group were determined and analyzed statistically. Results. The BPA oral intake at low and ten times higher dosage caused an increase of the number of sympathetic nerve fibers within the porcine liver by 48.6% and 63.7%, respectively. Moreover, BPA exposure caused an increased presence of sympathetic nerve fibers in these two experimental groups, which were co-localized with CART and GAL up to 65.9%/173.2% and 147.4%/126.3%, respectively. At the lower BPA doses of 50 μg/kg b.w./day, the percentages of SP+/DbH+ and CGRP+/DbH+ nerve fibers were similar to the control. 114Michael Thoene et al. However at a ten times higher dose, BPA caused an increased number of SP+/ DbH+ and CGRP+/ DbH+ nerve fibers in the liver, up to 46.4% and 73.5% respectively. Conclusions. BPA caused an increase in the number of sympathetic nerve fibers as well as sympathetic nerve fibers which co-localized with neuropeptides in the porcine liver. The increase in CART and GAL were exceptionally high even at low BPA doses. BPA food contamination may dysregulate liver sympathetic innervation, and thereby may change the oxygenated blood supply, alter metabolism and disrupt the activity of hepatic parenchymal cells.

show abstract

Suppressive Effects of Bisphenol A on the Proliferation of Neural Progenitor Cells

Cited by 59 publications

References 44 publications

Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway

Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway

Non-Monotonic Dose Responses in Studies of Endocrine Disrupting Chemicals: Bisphenol a as a Case Study

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

Contact Info

Product

Resources

About