Effect of melatonin on PCB (Aroclor 1254) induced neuronal damage and changes in Cu/Zn superoxide dismutase and glutathione peroxidase-4 mRNA expression in cerebral cortex, cerebellum and hippocampus of adult rats

Venkataraman, P.; Selvakumar, Kandaswamy; Giribabu, K.; Muthusami, Sridhar; Radhakrishnan, Ramalingam; Prakash, Seepan; Arunakaran, J.

doi:10.1016/j.neures.2009.10.015

Cited by 46 publications

(38 citation statements)

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“…), Group II: Rats were treated with PCBs (Aroclor 1254)-2 mg/kg bwt (i.p) [40], Group III: Rats were simultaneously treated with PCBs (Aroclor 1254)-2 mg/kg bwt (i.p) and melatonin-5 mg/kg bwt (i.p) [41], Group IV: Rats were treated with melatonin alone 5 mg/kg bwt (i.p) [41] to check the side effect of melatonin. PCBs were dissolved in corn oil, while melatonin was dissolved in 0.9 % saline plus 2 % ethanol.…”

Section: Experimental Procedures Animal Modelmentioning

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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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: Experimental Procedures Animal Modelmentioning

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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“…Earlier studies in our laboratory Venkataraman et al [58] found that PCB cause degeneration of pyramidal cells in hippocampus in PCB treated rats. Induction of NFkB and TNFa, after PCB exposure plays a critical role on neurodegeneration.…”

Section: Discussionmentioning

confidence: 87%

“…The damage in other regions such as cerebral cortex and cerebellum is also evident. In our earlier studies also neuronal damages were observed in all the brain regions [58]. Oxidative damage is due its high oxygen consumption, presence of high levels of polyunsaturated fatty acids (PUFA) and non regenerative nature of neurons which may lead to various neurogenerative diseases.…”

Section: Discussionmentioning

confidence: 91%

“…Group 2 rats received quercetin by gavage at a dose of 50 mg kg -1 bwt [29]. Group 3 rats received i.p injection of Aroclor 1254 at a dose of 2 mg kg -1 bwt [30] and Group 4 rats were administered with Aroclor 1254 at a dose of 2 mg kg -1 bwt (i.p.) and simultaneously quercetin was supplemented by gavage at a dose of 50 mg kg -1 bwt.…”

Section: Treatmentsmentioning

confidence: 99%

“…The paraffin blocks were cut into 10 lm thickness using rotary microtome. The sections were stained with haematoxylin and eosin [30]. The hippocampus morphology was analyzed by Nikon Microscope Eclipse 80i (109 and 209 magnifications).…”

Section: Histologymentioning

confidence: 99%

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Protective Role of Quercetin on PCBs-Induced Oxidative Stress and Apoptosis in Hippocampus of Adult Rats

et al. 2011

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Polychlorinated biphenyls (PCBs) exposure produces neurodegeneration and induces oxidative stress. Neuroprotective role of quercetin, on PCBs induced apoptosis in hippocampus has not yet been studied. The present study is focused to see whether quercetin supplementation precludes against PCBs induced oxidative stress and hippocampal apoptosis. The results have shown that quercetin at 50 mg/kg bwt/30 days has protected oxidative stress in hippocampus of adult male rats. Quercetin, a free radical scavenger decreased the levels of oxidative stress markers in the hippocampus of simultaneous PCB+quercetin treated rats. The pro-apoptotic and anti-apoptotic molecules such as Bad, Bid, Bax and Bcl2 were altered in the hippocampus of experimental animals. PCBs increased the DNA damage and induced neurodegeneration were assessed by histological studies. PCB induced ROS may be linked to increased hippocampal neuronal apoptosis. Quercetin supplementation decreased the neuronal damage and scavenged the free radicals induced by PCBs and protects PCBs induced apoptosis and oxidative stress.

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Extracellular signal‐related kinase 2/specificity protein 1/specificity protein 3/repressor element‐1 silencing transcription factor pathway is involved in Aroclor 1254‐induced toxicity in SH‐SY5Y neuronal cells

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et al. 2014

J of Neuroscience Research

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Polychlorinated biphenyls (PCBs) cause a wide spectrum of toxic effects in the brain through undefined mechanisms. Exposure to the PCB mixture Aroclor-1254 (A1254) increases the repressor element-1 silencing transcription factor (REST) expression, leading to neuronal death. This study sought to understand the sequence of some molecular mechanisms to determine whether A1254 could increase REST expression and the cytoprotective effect of the phorbol ester tetradecanoylphorbol acetate (TPA) on A1254-induced toxicity in SH-SY5Y cells. As shown by Western blot analysis, A1254 (10 µg/ml) downregulates extracellular signal-related kinase 2 (ERK2) phosphorylation in a time-dependent manner, thereby triggering the binding of specificity protein 1 (Sp1) and Sp3 to the REST gene promoter as revealed by chromatin immunoprecipitation analysis. This chain of events results in an increase in REST mRNA and cell death, as assessed by quantitative real-time polymerase chain reaction and dimethylthiazolyl-2-5-diphenyltetrazolium-bromide assay, respectively. Accordingly, TPA prevented both the A1254-induced decrease in ERK2 phosphorylation and the A1254-induced increase in Sp1, Sp3, and REST protein expression. After 48 hr, TPA prevented A1254-induced cell death. ERK2 overexpression counteracted the A1254-induced increase in Sp1 and Sp3 protein expression and prevented A1254-induced Sp1 and Sp3 binding to the REST gene promoter, thus counteracting the increase in REST mRNA expression induced by the toxicant. In neuroblastoma SH-SY5Y cells, ERK2/Sp1/SP3/REST is a new pathway underlying the neurotoxic effect of PCB. The ERK2/Sp1/Sp3/REST pathway, which underlies A1254-induced neuronal death, might represent a new drug signaling cascade in PCB-induced neuronal toxicity.

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Effect of melatonin on PCB (Aroclor 1254) induced neuronal damage and changes in Cu/Zn superoxide dismutase and glutathione peroxidase-4 mRNA expression in cerebral cortex, cerebellum and hippocampus of adult rats

Cited by 46 publications

References 47 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

Protective Role of Quercetin on PCBs-Induced Oxidative Stress and Apoptosis in Hippocampus of Adult Rats

Extracellular signal‐related kinase 2/specificity protein 1/specificity protein 3/repressor element‐1 silencing transcription factor pathway is involved in Aroclor 1254‐induced toxicity in SH‐SY5Y neuronal cells

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