Polychlorinated biphenyls induced oxidative stress mediated neurodegeneration in hippocampus and behavioral changes of adult rats: Anxiolytic-like effects of quercetin

Selvakumar, Kandaswamy; Bavithra, Senthamilselvan; Lakshmanan, Ganesh; Giribabu, K.; Venkataraman, P.; Arunakaran, J.

doi:10.1016/j.toxlet.2013.06.237

Cited by 39 publications

(25 citation statements)

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“…Previous studies in our laboratory suggests that PCBs induces oxidative stress leading to neuronal apoptosis and alternative death pathways [31], disrupts dopaminergic system and calcium homeostatsis in cerebral cortex and cerebellum of rats [32,33]. Repeated exposure of adult rats to Aroclor 1254 induces neuronal injury and impaires the neurochemical manifestations of the NMDA receptor-mediated intracellular signaling in the hippocampus [28].…”

Section: Discussionmentioning

confidence: 89%

“…Earlier studies in our laboratory reported that PCBs exposure impairs tight junctional proteins [31] and causes disruption of dopaminergic system in cerebral cortex and cerebellum of rat via the production of reactive oxygen species (ROS) [32,33]. PCBs-induced ROS production leads to oxidative/ nitrosative stress and cell death through over-activation of NMDARs both in culture and in animal models [34].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Melatonin on Glutamate: BDNF Signaling in the Cerebral Cortex of Polychlorinated Biphenyls (PCBs)—Exposed Adult Male Rats

et al. 2015

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Various epidemiological survey suggests that the central nervous system is the target for many environmental contaminants. One among them is Aroclor 1254, a mixture of polychlorinated biphenyls (PCBs) which explore a spectrum of biochemical and neurotoxic responses in humans and laboratory animals. Learning and motor coordination deficits are the profound effects of PCBs which may be related to cerebral dysfunction. The aim of the study is to elicit the protective effect of melatonin (Mel), a potent, blood brain permeable antioxidant against the effect of Aroclor 1254 on the signaling of glutamate-principal excitatory neurotransmitter and brain derived neurotrophic factor (BDNF) in the cerebral cortex of adult rats which plays a key role in brain functions. Adult male Wistar rats were grouped into four and treated intraperitonealy (i.p) Group I with corn oil (Control), Group II with PCBs (2 mg/kg/bwt), Group III with PCBs + Mel (2 mg/kg/bwt + 5 mg/kg/bwt) and Group IV with Mel (5 mg/kg/bwt). The protein expression of glutamate signaling molecules and mRNA expressions of GLAST, BDNF signaling molecules were analyzed. The results suggest that simultaneous melatonin treatment significantly attenuated the NMDA receptor mediated glutamate excitotoxicity and protects the inhibition of BDNF signaling caused by PCBs exposure in cerebral cortex of adult male rats. Schematic pathway illustrating the proposed mechanism by which melatonin protects against A1254 mediated glutamate induced neurodegeneration in the cerebral cortex of adult male rats. PCBs induced neurodegeneration is caused by the overactivation of NMDAR, followed by the activation of voltage dependent calcium channels leading to the increase in intracellular Ca(2+) that stimulates calpain. Calpain inturn inhibits the PKA α and neurtrophin BDNF, its receptor and downstream signaling MAPK pathway leading to neurodegeneration. Melatonin had scavenged the ROS produced by PCBS and decreased the NMDAR expression which inturn protected the cells from neurodegeneration.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Effect of Melatonin on Glutamate: BDNF Signaling in the Cerebral Cortex of Polychlorinated Biphenyls (PCBs)—Exposed Adult Male Rats

et al. 2015

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“…Some PCBs can affect DA release and neurodegenerative processes that may also lead to cellular death (Fielding et al, 2013; Mariussen and Fonnum, 2001; Selvakumar et al, 2013). A PCB-induced reduction in brain 5HT levels has also been observed (Boix and Cauli, 2012; Honma et al, 2009).…”

Section: Polychlorinated Biphenylsmentioning

confidence: 99%

Current concepts in neuroendocrine disruption

León-Olea

Martyniuk

Orlando

et al. 2014

General and Comparative Endocrinology

126

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In the last few years, it has become clear that a wide variety of environmental contaminants have specific effects on neuroendocrine systems in fish, amphibians, birds and mammals. While it is beyond the scope of this review to provide a comprehensive examination of all of these neuroendocrine disruptors, we will focus on select representative examples. Organochlorine pesticides bioaccumulate in neuroendocrine areas of the brain that directly regulate GnRH neurons, thereby altering the expression of genes downstream of GnRH signaling. Organochlorine pesticides can also agonize or antagonize hormone receptors, adversely affecting crosstalk between neurotransmitter systems. The impacts of polychlorinated biphenyls are varied and in many cases subtle. This is particularly true for neuroedocrine and behavioral effects of exposure. These effects impact sexual differentiation of the hypothalamic-pituitary-gonadal axis, and other neuroendocrine systems regulating the thyroid, metabolic, and stress axes and their physiological responses. Weakly estrogenic and anti-androgenic pollutants such as bisphenol A, phthalates, phytochemicals, and the fungicide vinclozolin can lead to severe and widespread neuroendocrine disruptions in discrete brain regions, including the hippocampus, amygdala, and hypothalamus, resulting in behavioral changes in a wide range of species. Behavioral features that have been shown to be affected by one or more these chemicals include cognitive deficits, heightened anxiety or anxiety-like, sociosexual, locomotor, and appetitive behaviors. Neuroactive pharmaceuticals are now widely detected in aquatic environments and water supplies through the release of wastewater treatment plant effluents. The antidepressant fluoxetine is one such pharmaceutical neuroendocrine disruptor. Fluoxetine is a selective serotonin reuptake inhibitor that can affect multiple neuroendocrine pathways and behavioral circuits, including disruptive effects on reproduction and feeding in fish. There is growing evidence for the association between environmental contaminant exposures and diseases with strong neuroendocrine components, for example decreased fecundity, neurodegeneration, and cardiac disease. It is critical to consider the timing of exposures of neuroendocrine disruptors because embryonic stages of central nervous system development are exquisitely sensitive to adverse effects. There is also evidence for epigenetic and transgenerational neuroendocrine disrupting effects of some pollutants. We must now consider the impacts of neuroendocrine disruptors on reproduction, development, growth and behaviors, and the population consequences for evolutionary change in an increasingly contaminated world. This review examines the evidence to date that various so-called neuroendocrine disruptors can induce such effects often at environmentally-relevant concentrations.

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“…Acute and chronic exposure to polychlorinated biphenyls (PCBs) may induce neurotoxicity resulting in morphological changes of neurons, developmental defects of the nervous system, behavioral changes, and learning deficits (Winneke, 2011; Doi et al, 2013; Selvakumar et al, 2013; Lesiak et al, 2014). The blood–brain barrier (BBB) is a highly specialized structural and functional barrier separating the microenvironment of the central nervous system (CNS) from the peripheral circulation by restricting paracellular movement of ions and solutes across the brain endothelium (Dodelet-Devillers et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

Eum

Jaraki

András

et al. 2015

Toxicology and Applied Pharmacology

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Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2) after 24 h h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs.

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Polychlorinated biphenyls induced oxidative stress mediated neurodegeneration in hippocampus and behavioral changes of adult rats: Anxiolytic-like effects of quercetin

Cited by 39 publications

References 57 publications

Effect of Melatonin on Glutamate: BDNF Signaling in the Cerebral Cortex of Polychlorinated Biphenyls (PCBs)—Exposed Adult Male Rats

Effect of Melatonin on Glutamate: BDNF Signaling in the Cerebral Cortex of Polychlorinated Biphenyls (PCBs)—Exposed Adult Male Rats

Current concepts in neuroendocrine disruption

Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

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