Protective Effect of Curcumin by Modulating BDNF/DARPP32/CREB in Arsenic-Induced Alterations in Dopaminergic Signaling in Rat Corpus Striatum

• Published in: Molecular neurobiology Vol. 55; no. 1; pp. 445 - 461
• Main Authors: Srivastava, Pranay, Dhuriya, Yogesh K., Gupta, Richa, Shukla, Rajendra K., Yadav, Rajesh S., Dwivedi, Hari N., Pant, Aditya B., Khanna, Vinay K
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2018; Springer Nature B.V
• Subjects: Animals; Antioxidants; Antioxidants - metabolism; Apoptosis; Apoptosis - drug effects; Arsenic; Arsenic - toxicity; Biomedical and Life Sciences; Biomedicine; Body weight; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cell Biology; Cell Survival - drug effects; Corpus striatum; Corpus Striatum - pathology; Corpus Striatum - ultrastructure; Curcumin; Curcumin - pharmacology; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - metabolism; Dopamine - metabolism; Dopamine and cAMP-Regulated Phosphoprotein 32 - metabolism; Dopamine D2 receptors; Dopamine transporter; Exposure; Hydroxylase; Male; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Molecular modelling; Neostriatum; Neurobiology; Neurology; Neuroprotection; Neuroprotective Agents - pharmacology; Neurosciences; Protein kinase A; Proteins; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Receptors, Dopamine - metabolism; Rodents; Signal Transduction - drug effects; Tyrosine 3-monooxygenase; Vesicular monoamine transporter 2; Dopamine; CREB; Arsenic; BDNF; Corpus striatum; Curcumin; DARPP32
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-016-0288-2

Earlier, protective role of curcumin in arsenic-induced dopamine (DA)–D2 receptor dysfunctions in corpus striatum has been demonstrated by us. In continuation to that, the present study is focused to decipher the molecular mechanisms associated with alterations in dopaminergic signaling on arsenic exposure in corpus striatum and assess the protective efficacy of curcumin. Exposure to arsenic (20 mg/kg, body weight p.o. for 28 days) in rats resulted to decrease the expression of presynaptic proteins-tyrosine hydroxylase and VMAT2 while no effect was observed on the expression of DAT in comparison to controls. A significant decrease in the expression of DA-D2 receptors associated with alterations in the expression of PKA, pDARPP32 (Thr 34), and PP1 α was clearly evident on arsenic exposure. Expression of BDNF and pGSK3β in corpus striatum was found decreased in arsenic-exposed rats. Simultaneous treatment with curcumin (100 mg/kg, body weight p.o. for 28 days) resulted to protect arsenic-induced alterations in the expression of DA-D2 receptors, PKA, pDARPP32, pCREB, and pPP1α. Neuroprotective efficacy of curcumin can possibly be attributed to its antioxidant potential which significantly protected arsenic-induced mitochondrial dysfunctions by modulating the ROS generation and apoptosis. Modulation in the expression of BDNF and pGSK3β in corpus striatum by curcumin exhibits the importance of neuronal survival pathway in arsenic-induced dopaminergic dysfunctions. Interestingly, curcumin was also found to protect arsenic-induced ultrastructural changes in corpus striatum. The results exhibit that curcumin modulates BDNF/DARPP32/CREB in arsenic-induced alterations in dopaminergic signaling in rat corpus striatum.