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Brain-derived neurotrophic factor protects neurons from GdCl3-induced impairment in neuron-astrocyte co-cultures

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Abstract

Gadolinium (Gd3+) complexes are important contrast agents in medical magnetic resonance imaging (MRI) and of great potential value in brain research. In order to better understand the mechanisms of the action of Gd3+ on neurons in the complex central nervous system (CNS), the neurotoxic actions of GdCl3 have been investigated in both neuron monoculture and astrocyte-neuron co-culture systems. Measurements of lactate dehydrogenase release showed that GdCl3 causes significant cell death of monocultured neurons as a result of reactive oxygen species (ROS) generation and down-regulation of brain-derived neurotrophic factor (BDNF). However, GdCl3 does not affect the viability and BDNF expression of astrocytes. Both co-culturing of neurons with astrocytes and addition of BDNF ameliorated GdCl3-induced neurotoxicity by decreasing ROS generation and facilitating recovery of BDNF levels. The results obtained suggest that astrocytes in the CNS may protect neurons from GdCl3-induced impairment through secreting BDNF and thus up-regulating BDNF expression and interfering with Gd3+-induced cell signaling in neurons. A possible molecular mechanism is suggested which should be helpful in understanding the neurotoxic actions of gadolinium probes.

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References

  1. Bellin MF, van der Molen AJ. Extracellular gadolinium-based contrast media: An overview. Eur J Radiol, 2008, 66: 160–167

    Article  Google Scholar 

  2. Xia Q, Han HB. The diffusion of Gd-DTPA in brain ECS studied by MRI. J Biol Inorg Chem, 2009, 14(Suppl 1): S162 (P254)

    Google Scholar 

  3. Abraham JL, Thakral C, Skov L, Rossen K, Marckmann P. Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis. Br J Dermatol, 2008, 158: 273–280

    Article  CAS  Google Scholar 

  4. Fan G, Yuan Z, Zheng H, Liu Z. Study on the effects of exposure to rare earth elements and health-responses in children aged 7–10 years (in Chinese). J Hyg Res, 2004, 33: 23–28

    Google Scholar 

  5. Zhu WF, Xu SQ, Shao PP, Zhang H, Feng J, Wu DS, Yang WJ. Investigation of children intelligence quotient in REE mining area: Bio-effect study of REE mining area in South Jiangxi. Chin Sci Bull, 1996, 41: 914–916

    Google Scholar 

  6. Feng L, Xiao H, He X, Li Z, Lia F, Liu N, Zhao Y, Huang Y, Zhang Z, Chai Z. Neurotoxicological consequence of long-term exposure to lanthanum. Toxicol Lett, 2006, 165: 112–120

    Article  CAS  Google Scholar 

  7. Yang W, Zhang P, Liu J, Xue Y. Effect of long-term intake of Yb3+ in drinking water on gene expression in brains of rats. J Rare Earths, 2006, 24: 369–373

    Article  Google Scholar 

  8. Ray D E, Holton J, Nolan CC. Neurotoxic potential of gadodiamide after injection into the lateral cerebral ventricle of rats. Am J Neuroradiol, 1998, 19: 1455–1462

    CAS  Google Scholar 

  9. Toney GM, Chavez HA, Ibarra R. Acute and subacute physiological and histological studies of the central nervous system after intrathecal gadolinium injection in the anesthetized rat. Invest Radiol, 2001, 36: 33–40

    Article  CAS  Google Scholar 

  10. Ricci G, Volpi L, Pasquali L, Petrozzi L, Siciliano G. Astrocyte-neuron interactions in neurological disorders. J Biol Phys, 2009, 35: 317–336

    Article  CAS  Google Scholar 

  11. Legare ME, Barhoumi R, Hebert E, Bratton GR, Burghardt RC, Tiffany-Castiglioni E. Analysis of Pb2+ entry into cultured astroglia. Toxicol Sci, 1998, 46: 90–100

    CAS  Google Scholar 

  12. Dhandapani KM, Brann DW. Role of astrocytes in estrogen-mediated neuroprotection. Exp Gerontol, 2007, 42: 70–75

    Article  CAS  Google Scholar 

  13. Arancibia S, Silhol M, Moulière F, Meffre J, Höllinger I, Maurice T, Tapia-Arancibia L. Protective effect of BDNF against β-amyloid induced neurotoxicity in vitro and in vivo in rats. Neurobiol Dis, 2008, 31: 316–326

    Article  CAS  Google Scholar 

  14. Kirschner PB, Jenkins BG, Schulz JB, Finkelstein SP, Matthews RT, Rosen BR, Beal MF. NGF, BDNF and NT-5, but not NT-3 protect against MPP+ toxicity and oxidative stress in neonatal animals. Brain Res, 1996, 713: 178–185

    Article  CAS  Google Scholar 

  15. Kume T, Kouchiyama H, Kaneko S, Maeda T, Kaneko S, Akaike A, Shimohama S, Kihara T, Kimura J, Wada K, Koizumi S. BDNF prevents NO mediated glutamate cytotoxicity in cultured cortical neurons. Brain Res, 1997, 756: 200–204

    Article  CAS  Google Scholar 

  16. Petersén AA, Larsen KE, Behr GG, Romero N, Przedborski S, Brundin P, Sulzer D. Brain-derived neurotrophic factor inhibits apoptosis and dopamine-induced free radical production in striatal neurons but does not prevent cell death. Brain Res Bull, 2001, 56: 331–335

    Article  Google Scholar 

  17. Liu H, Yuan L, Yang X, Wang K. La3+, Gd3+, and Yb3+ induced changes in mitochondrial structure, membrane permeability, cytochrome c release and intracellular ROS level. Chem-Biol Interact, 2003, 146: 27–37

    Article  CAS  Google Scholar 

  18. Dong S, Zhao Y, Liu H, Yang X, Wang K. Duality of effect of La3+ on mitochondrial permeability transition pore depending on the concentration. BioMetals, 2009, 22: 917–926

    Article  CAS  Google Scholar 

  19. Dugan LL, Bruno VM, Amagasu SM, and Giffard RG. Glia modulate the response of murine corticalneurons to excitotoxicity: glia exacerbate AMPA neurotoxicity. J Neurosci, 15: 4545–4555

  20. Morken TS, Sonnewald U, Aschner M, Syversen T. Effects of methylmercury on primary brain cells in mono- and co-culture. Toxicol Sci, 2005, 87: 169–175

    Article  CAS  Google Scholar 

  21. Raghavamenon AC, Gernapudi R, Babu S, D’Auvergne O, Murthy SN, Kadowitz PJ, Uppu RM. Intracellular oxidative stress and cytotoxicity in rat primary cortical neurons exposed to cholesterol secoaldehyde. Biochem Biophys Res Commun, 2009, 386: 170–174

    Article  CAS  Google Scholar 

  22. Li XA, Lee AS. Competitive inhibition of a set of endoplasmic reticulum protein genes (GRP78, GRP94, and ERp72) retards cell growth and lowers viability after ionophore treatment. Mol Cell Biol, 1991, 11: 3446–3453

    CAS  Google Scholar 

  23. Kumar R, Agarwal AK, Seth PK. Oxidative stress-mediated neurotoxicity of cadmium. Toxicol Lett, 1996, 89: 65–69

    Article  CAS  Google Scholar 

  24. Leonard SS, Harris GK, Shi X. Metal-induced oxidative stress and signal transduction. Free Radical Bio Med, 2004, 37: 1921–1942

    Article  CAS  Google Scholar 

  25. Wang K, Cheng Y, Yang X, Li R. Cell responses to lanthanides and potential pharmacological actions of lanthanides. Metal Ions Biol Syst, 2003, 40: 707–751

    CAS  Google Scholar 

  26. Markham A, Cameron I, Franklin P, Spedding M. BDNF increases rat brain mitochondrial respiratory coupling at complex I, but not complex II. Eur J Neurosci, 2004, 20: 1189–1196

    Article  CAS  Google Scholar 

  27. Jackson GR, Apffel L, Werrbach-Perez K, Perez-Polo JR. Role of nerve growth factor in oxidant-antioxidant balance and neuronal injury. I. Stimulation of hydrogen peroxide resistance. J Neurosci Res, 1990, 25: 360–368

    Article  CAS  Google Scholar 

  28. Aharoni R, Eilam R, Domev H, Labunskay G, Sela M, Arnon R. The immunomodulator glatiramer acetate augments the expression of neurotrophic factors in brains of experimental autoimmune encephalomyelitis mice. Proc Nat Acad Sci, 2005, 102: 19045–19050

    Article  CAS  Google Scholar 

  29. Toyomoto M, Ohta M, Okumura K, Yano H, Matsumoto K, Inoue S, Hayashi K, Ikeda K. Prostaglandins are powerful inducers of NGF and BDNF production in mouse astrocyte cultures. FEBS Lett, 2004, 562: 211–215

    Article  CAS  Google Scholar 

  30. Feng XD, Xia Q, Liu HX, Han HB, Yang X, Wang K. The mechanism of actions of gadolinium chloride (GdCl3) on neurons. J Biol Inorg Chem, 2009, 14(Suppl 1): S119 (P063)

    Google Scholar 

  31. Shen C, Li Z, Yang X., Wang K. La3+ binds to BiP/GRP78 and induces unfolded protein response in HepG2 cells. Chem-Biol Interact, 2008, 176: 196–203

    Article  CAS  Google Scholar 

  32. Saha RN, Liu X, Pahan K. Up-regulation of BDNF in astrocytes by TNF-α: A case for the neuroprotective role of cytokine. J Neuroimmune Pharmacol, 2006, 1: 212–222

    Article  Google Scholar 

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Correspondence to Qing Xia or XiaoDa Yang.

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Xia, Q., Feng, X., Yuan, L. et al. Brain-derived neurotrophic factor protects neurons from GdCl3-induced impairment in neuron-astrocyte co-cultures. Sci. China Chem. 53, 2193–2199 (2010). https://doi.org/10.1007/s11426-010-4105-x

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