Role of Quercetin on PCBs (Aroclor-1254) Induced Impairment of Dopaminergic Receptor mRNA Expression in Cerebral Cortex of Adult Male Rats

Kumari, Rasiah Pratheepa; Selvakumar, Kandaswamy; Bavithra, Senthamilselvan; Zumaana, Rafiq; Giribabu, K.; Arunakaran, J.

doi:10.1007/s11064-011-0449-7

Cited by 17 publications

(10 citation statements)

References 40 publications

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“…Thus Glutamate-BDNF signaling alterations may be one of the reasons of PCBs induced neurodegeneration in cerebral cortex which has been reported in our earlier studies [32,41] …”

Section: Discussionsupporting

confidence: 64%

“…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: 88%

“…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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“…Thus Glutamate-BDNF signaling alterations may be one of the reasons of PCBs induced neurodegeneration in cerebral cortex which has been reported in our earlier studies [32,41] …”

Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 88%

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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“…Therefore, PCBs has effect on TH at the level of translation and not on transcription. There is a significant down regulation of D 2 -like receptor expression and up regulation of D 1 -like receptor expression in the cerebellum of PCBs treated group at both the levels of transcription and translation, similar results at the level of transcription was observed in cerebral cortex also (Pratheepa kumari et al 2011). The change in brain (cerebellum) dopamine content due to PCBs exposure could be responsible of the alteration in protein expression, by an adaptive mechanism, after long term exposure to PCBs.…”

supporting

confidence: 68%

Polychlorinated Biphenyl (PCBs)-Induced Oxidative Stress Plays a Critical Role on Cerebellar Dopaminergic Receptor Expression: Ameliorative Role of Quercetin

et al. 2011

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Polychlorinated biphenyls (PCBs) exposure produces profound damage to the developing as well as adult central nervous system. Locomotor activities which are closely linked to dopaminergic neurotransmission are often impaired in PCBs toxicity. Targeting PCBs-induced oxidative stress using natural antioxidants is an attractive approach. Quercetin, a flavonoid is a safe and potent neuroprotective antioxidant. In this study, we sought to examine the protective role of quercetin against PCBs-induced neurodegeneration and dysfunction of dopaminergic receptors in the cerebellar region of adult male rats. They were divided into four groups. Group I received only vehicle (corn oil) intraperitoneally (i.p); Group II received Aroclor 1254 at a dose of 2 mg/kg bwt/day (i.p); Group III received Aroclor 1254 (i.p) and simultaneously quercetin (50 mg/kg bwt/day) through gavage; Group IV received quercetin alone (gavage). After 30 days treatment, rats were euthanized. The cerebellum was dissected from each rat brain, the levels of hydrogen peroxide, lipid peroxidation, protein carbonyl content, and activities of creatine kinase, acetylcholine esterase, membrane-bound ATPases were evaluated. Expressions of dopaminergic receptors and tyrosine hydroxylase in cerebellum were studied by semi-quantitative RT-PCR and western blot analysis, respectively. The PCBs-induced neurodegeneration was assessed by histological studies. Results proclaim that PCBs disturb dopaminergic receptors and also causes neurodegeneration in cerebellum via production of ROS. Simultaneous quercetin treatment had scavenged the free radicals induced by PCBs and protected dopaminergic receptors dysfunction in rat cerebellum.

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“…Quercetin has been reported to be effective in prevention of oxidative damage to DNA or to cell membrane [54]. One of the mechanism is that quercetin may stabilize lipid membranes and protect lipid peroxidation by free radicals scavenging mechanism thereby protecting tissues as evidenced in our earlier studies on rat seminal vesicles and ventral prostate [39, 40].…”

Section: Discussionmentioning

confidence: 99%

Polychlorinated Biphenyls-Induced Oxidative Stress on Rat Hippocampus: A Neuroprotective Role of Quercetin

Selvakumar

Bavithra

Giribabu

et al. 2012

The Scientific World Journal

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Present study is aimed to evaluate the ameliorative role of quercetin on PCBs-induced oxidative stress in hippocampus of Wistar rats. Group I rats received vehicle (corn oil) intraperitoneally (i.p); Group II received quercetin 50 mg/kg bwt/day (gavage); Group III received PCB 2 mg/kg bwt/day (i.p); Group IV received PCB (i.p) and simultaneously quercetin through gavage. After 30 days, rats were euthanized and hippocampus was dissected from each rat brain. Oxidative stress was assessed by determining the levels of H2O2, LPO, Pcc, and alteration in the functional markers such as CK, AchE, and ATPases activities in the hippocampus of control and experimental animals. A significant increase in the levels of stress markers and decrease in level of functional markers were observed in PCBs-treated rats. Moreover DNA fragmentation and histological studies were ascertained to confirm PCBs toxicity. In conclusion, quercetin shows a protective role against PCBs-induced oxidative damage in rat hippocampus.

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Role of Quercetin on PCBs (Aroclor-1254) Induced Impairment of Dopaminergic Receptor mRNA Expression in Cerebral Cortex of Adult Male Rats

Cited by 17 publications

References 40 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

Polychlorinated Biphenyl (PCBs)-Induced Oxidative Stress Plays a Critical Role on Cerebellar Dopaminergic Receptor Expression: Ameliorative Role of Quercetin

Polychlorinated Biphenyls-Induced Oxidative Stress on Rat Hippocampus: A Neuroprotective Role of Quercetin

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