Guoying Bing
Connect
859-323-9708gbing@uky.edu
Positions
- Professor
- Regular Faculty
College Unit(s)
Other Affiliation(s)
- Diversity Departmental Ambassadors
Research
Neuroinflammation Mediated Dopaminergic Cell Death
Parkinson’s Disease (PD) is a neurodegenerative disease characterized by loss of the dopamine-containing neurons in the substantia nigra pars compacta (SNpc). Although the cause of neuronal death remains unclear, increasing evidence points to the role of chronic inflammatory processes. In order to explore the possibility that microglial activation causes dopaminergic cell death in the SNpc, lipopolysaccharide (LPS), a bacterial endotoxin that activate microglia, was into the substantia nigra (SN). The LPS injection not only caused the activation of microglia, but also resulted in a dose-dependent, selective loss of dopaminergic neurons by apoptosis in the SNpc. We therefore hypothesize that LPS activates microglia in the SN resulting in the release of cytotoxic agents. These agents, in turn, activate signal transduction pathways that cause neuronal degeneration of dopaminergic neurons in the SN. The long-term goal of this study is to validate LPS injection as a new animal model of PD that can be used to elucidate the etiology and molecular mechanisms underlying PD and to develop novel therapeutic treatments for this and other neurodegenerative diseases.
Influence of Xenobiotic Metabolites on the Neuronal Cell Death
Dr. Bing’s laboratory has recently found that a high level of microsomal epoxide hydrolase (mEH) expression in the brain of patients with Alzheimer’s disease as well as the rat brain following exposure to neurodegenerative agents such as kainic acid and trimethyl-tin. Relatively little is known about the expression and function of mEH in the CNS. However, the dual function of mEH in the activation as well as the inactivation of various reactive compounds from xenobiotic metabolites has important implications regarding its role in brain toxicity. The hypothesize is that mEH plays a crucial role in the biotransformation of endogenous xenobiotics and/or environmental chemicals into more toxic metabolites which may cause neuronal degeneration in specific neuronal populations. The identifying the exact role of mEH as well as the role of xenobiotic metabolites in the brain will be critical in understanding the neurodegeneration induced by exposure to toxic chemicals.
Selected Publications
1. Choi DY, Zhang J, Bing G. Aging enhances the neuroinflammatory response and alpha-synuclein nitration in rats. Neurobiol Aging. 2010, 31(9):1649-53. PMID: 18986737
2. Xing B, Xin T, Zhao L, Hunter RL, Chen Y, Bing G. Glial cell line-derived neurotrophic factor protects midbrain dopaminergic neurons against lipopolysaccharide neurotoxicity. J Neuroimmunol. 2010, 25;225(1-2):43-51. PMCID: PMC2924924.PMID: 20471698
3. Liu M, Choi DY, Hunter RL, Pandya JD, Cass WA, Sullivan PG, Kim HC, Gash DM, Bing G. Trichloroethylene induces dopaminergic neurodegeneration in Fisher 344 rats. J Neurochem. 2010, 112(3):773-83. PMID: 19922440
4. Nguyen XV, Liu M, Kim HC, Bing G. Effects of prodynorphin deletion on striatal dopamine in mice during normal aging and in response to MPTP. Exp Neurol. 2009, 219(1):228-38. Epub 2009 Jun 3. PMID: 19500577
5. Hunter RL, Cheng B, Choi DY, Liu M, Liu S, Cass WA, Bing G. Intrastriatal lipopolysaccharide injection induces parkinsonism in C57/B6 mice. J Neurosci Res. 2009, 87(8):1913-21. PMCID: PMC2692550, PMID: 19224579
6. Choi DY, Liu M, Hunter RL, Cass WA, Pandya JD, Sullivan PG, Shin EJ, Kim HC, Gash DM, Bing G. Striatal neuroinflammation promotes Parkinsonism in rats. PLoS One. 2009, 4(5):e5482. Epub 2009 May 8. PMCID: PMC2674956, PMID: 19424495
7. Liu M, Hunter R, Nguyen XV, Kim HC, Bing G. Microsomal epoxide hydrolase deletion enhances tyrosine hydroxylase phosphorylation in mice after MPTP treatment. J Neurosci Res. 2008, 86(12):2792-801. PMID: 18500758
8. Hunter RL, Liu M, Choi DY, Cass WA, Bing G. Inflammation and age-related iron accumulation in F344 rats. Curr Aging Sci. 2008, 1(2):112-21. PMID: 20021380
9. Hunter RL, Choi DY, Ross SA, Bing G. Protective properties afforded by pioglitazone against intrastriatal LPS in Sprague-Dawley rats. Neurosci Lett. 2008, 432(3):198-201. PMCID: PMC2699576, PMID: 18207323
10. Gash DM, Rutland K, Hudson NL, Sullivan PG, Bing G, Cass WA, Pandya JD, Liu M, Choi DY, Hunter RL, Gerhardt GA, Smith CD, Slevin JT, Prince TS. Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity. Ann Neurol. 2008, 63(2):184-92. PMID:18157908
11. Xing B, Xin T, Hunter RL, Bing G. Pioglitazone inhibition of lipopolysaccharide-induced nitric oxide synthase is associated with altered activity of p38 MAP kinase and PI3K/Akt. J Neuroinflammation. 2008, 5:4. PMCID: PMC2254610, PMID:18205920
12. Hunter RL, Bing, G. Agonism of peroxisome proliferator receptor-gamma may have therapeutic potential for neuroinflammation and Parkinson's disease. Current Neuropharmacology. 2007, 5(1): 35-46.
13. Xing B, Liu M, Bing G. Neuroprotection with pioglitazone against LPS insult on dopaminergic neurons may be associated with its inhibition of NF-kappaB and JNK activation and suppression of COX-2 activity. J Neuroimmunol. 2007, 192(1-2):89-98. PMID: 17976742
14. Hunter RL, Dragicevic N, Seifert K, Choi DY, Liu M, Kim HC, Cass WA, Sullivan PG, Bing G. Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. J Neurochem. 2007, 100(5):1375-86. PMID: 17254027
15. Arimoto T, Choi DY, Lu X, Liu M, Nguyen XV, Zheng N, Stewart CA, Kim HC, Bing G. Interleukin-10 protects against inflammation-mediated degeneration of dopaminergic neurons in substantia nigra. Neurobiol Aging. 2007, 28 (6): 894-906. PMID: 16769155.
2006, Jun 10; [Epub ahead of print] PMID: 16769155
16. Bing G, Nguyen XV, Liu M, Markesbery WR, Sun A. Biophysical and biochemical characterization of the intrinsic fluorescence from neurofibrillary tangles. Neurobiol Aging. 2006. PMID: 15946772
17. Liu M, Sun A, Shin EJ, Liu X, Kim SG, Runyons CR, Markesbery W, Kim HC, Bing G. Expression of microsomal epoxide hydrolase is elevated in Alzheimer's hippocampus and induced by exogenous beta-amyloid and trimethyl-tin. Eur J Neurosci. 2006, 23(8):2027-34. PMID: 16630050
18. Vijitruth R, Liu M, Choi DY, Nguyen XV, Hunter RL, Bing G. Cyclooxygenase-2 mediates microglial activation and secondary dopaminergic cell death in the mouse MPTP model of Parkinson's disease. J Neuroinflammation. 2006, 3:6. PMCID: PMC1440849, PMID: 16566823
19. Nguyen XV, Masse J, Kumar A, Vijitruth R, Kulik C, Liu M, Choi DY, Foster TC, Usynin I, Bakalkin G, Bing G. Prodynorphin knockout mice demonstrate diminished age-associated impairment in spatial water maze performance. Behav Brain Res. 2005, 161(2):254-62. PMID: 15922052
20. Zhang J, Stanton DM, Nguyen XV, Liu M, Zhang Z, Gash D, Bing G. Intrapallidal lipopolysaccharide injection increases iron and ferritin levels in glia of the rat substantia nigra and induces locomotor deficits. Neuroscience. 2005, 135(3):829-38. PMID: 16165292
21. Sun A, Liu M, Nguyen XV, Bing G. P38 MAP kinase is activated at early stages in Alzheimer's disease brain. Exp Neurol. 2003, 183(2):394-405. PMID: 14552880
22. Liou YC, Sun A, Ryo A, Zhou XZ, Yu ZX, Huang HK, Uchida T, Bronson R, Bing G, Li X, Hunter T, Lu KP. Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration. Nature. 2003, 424(6948):556-61. PMID: 12891359
23. Arimoto T, Bing G. Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration. Neurobiol Dis. 2003, 12(1):35-45. PMID: 12609487
24. Sun A, Koelsch G, Tang J, Bing G. Localization of beta-secretase memapsin 2 in the brain of Alzheimer's patients and normal aged controls. Exp Neurol. 2002, 175(1):10-22. PMID: 12009756
25. Kim HC, Bing G, Jhoo WK, Kim WK, Shin EJ, Park ES, Choi YS, Lee DW, Shin CY, Ryu JR, Ko KH. Oxidative damage causes formation of lipofuscin-like substances in the hippocampus of the senescence-accelerated mouse after kainate treatment. Behav Brain Res. 2002, 131(1-2):211-20. PMID: 11844588
26. Sun A, Nguyen XV, Bing G. Comparative analysis of an improved thioflavin-s stain, Gallyas silver stain, and immunohistochemistry for neurofibrillary tangle demonstration on the same sections. J Histochem Cytochem. 2002, 50(4):463-72. PMID: 11897799
27. Sun A, Nguyen XV, Bing G. A novel fluorescent method for direct visualization of neurofibrillary pathology in Alzheimer's disease. J Neurosci Methods. 2001, 111(1):17-27. PMID:
28. Feng Z, Hong J, Qi Q, Han Y, Wilson B, Iadarola M, Tiao N, Bing G. Cloning and expression of MP13 gene from rat hippocampus, a new factor related to guanosine triphosphate regulation. Neurosci Lett. 2000, 296(2-3):129-32. PMID: 11108998
29. Kim H, Jhoo W, Shin E, Bing G. Selenium deficiency potentiates methamphetamine-induced nigral neuronal loss; comparison with MPTP model. Brain Res. 2000, 862(1-2):247-52. PMID:
30. Floyd RA, Hensley K, Bing G. Evidence for enhanced neuro-inflammatory processes in neurodegenerative diseases and the action of nitrones as potential therapeutics. J Neural Transm Suppl. 2000, (60):387-414. Review. PMID: 11205157
31. Lu X, Bing G, Hagg T. Naloxone prevents microglia-induced degeneration of dopaminergic substantia nigra neurons in adult rats. Neuroscience. 2000;97(2):285-91. PMID: 10799760
32. Kim HC, Jhoo WK, Choi DY, Im DH, Shin EJ, Suh JH, Floyd RA, Bing G. Protection of methamphetamine nigrostriatal toxicity by dietary selenium. Brain Res. 1999, 851(1-2):76-86. PMID: 10642830
33. Hensley K, Floyd RA, Zheng NY, Nael R, Robinson KA, Nguyen X, Pye QN, Stewart CA, Geddes J, Markesbery WR, Patel E, Johnson GV, Bing G. p38 kinase is activated in the Alzheimer's disease brain. J Neurochem. 1999, 72(5):2053-8. PMID: 10217284
34. Gupta RP, Bing G, Hong JS, Abou-Donia MB. cDNA cloning and sequencing of Ca2+/calmodulin-dependent protein kinase IIalpha subunit and its mRNA expression in diisopropyl phosphorofluoridate (DFP)-treated hen central nervous system. Mol Cell Biochem. 1998, 181(1-2):29-39. PMID: 9562239
35. Bing G, Wilson B, Hudson P, Jin L, Feng Z, Zhang W, Bing R, Hong JS. A single dose of kainic acid elevates the levels of enkephalins and activator protein-1 transcription factors in the hippocampus for up to 1 year. Proc Natl Acad Sci USA 1997, 94(17):9422-7. PMCID: PMC23206, PMID: 9256498
36. Bing G, Wang W, Qi Q, Feng Z, Hudson P, Jin L, Zhang W, Bing R, Hong JS. Long-term expression of Fos-related antigen and transient expression of delta FosB associated with seizures in the rat hippocampus and striatum. J Neurochem. 1997, 68(1):272-9. PMID: 8978735
37. Bing G, Wilson B, McMillian M, Feng Z, Qi Q, Kim H, Wang W, Jensen K, Hong JS. Long-term expression of Proenkephalin and prodynorphin in the rat brain after systemic administration of kainic acid, an in situ hybridization study. In Neurodegenerative Disease, ed. by G. Flskum, Plenum Press, 1996, pp 8-18.
38. Bing G, McMillian M, Kim H, Pennypacker K, Feng Z, Qi Q, Kong LY, Iadarola M, Hong JS. Long-term expression of the 35,000 mol. wt fos-related antigen in rat brain after kainic acid treatment. Neuroscience. 1996, 73(4):1159-74. PMID: 8809832
39. McMillian M, Kong LY, Sawin SM, Wilson B, Das K, Hudson P, Hong JS, Bing G. Selective killing of cholinergic neurons by microglial activation in basal forebrain mixed neuronal/glial cultures. Biochem Biophys Res Commun. 1995, 215(2):572-7. PMID: 7487994
40. Bing G, Zhang Y, Watanabe Y, McEwen BS, Stone EA. Locus coeruleus lesions potentiate neurotoxic effects of MPTP in dopaminergic neurons of the substantia nigra. Brain Res. 1994, 668(1-2):261-5. PMID: 7704612
41. Stone EA, Manavalan JS, Basham DA, Bing G. Effect of yohimbine on nerve growth factor mRNA and protein levels in rat hippocampus. Neurosci Lett. 1994, 167(1-2):11-3. PMID: 8177507
42. Stone EA, Zhang Y, John S, Filer D, Bing G. Effect of locus coeruleus lesion on c-fos expression in the cerebral cortex caused by yohimbine injection or stress. Brain Res. 1993, 603(2):181-5. PMID: 8461977
43. Bing G, Stone EA, Zhang Y, Filer D. Immunohistochemical studies of noradrenergic-induced expression of c-fos in the rat CNS. Brain Res. 1992, 592(1-2):57-62. PMID: 1360316
44. Bing G, Chen S, Zhang Y, Hillman D, Stone EA. Noradrenergic-induced expression of c-fos in rat cortex: neuronal localization. Neurosci Lett. 1992, 140(2):260-4. PMID: 1501788
45. Stone EA, Zhang Y, John SM, Bing G. c-Fos response to administration of catecholamines into brain by microdialysis. Neurosci Lett. 1991, 133(1):33-5. PMID: 1791995
46. Bing GY, Filer D, Miller JC, Stone EA. Noradrenergic activation of immediate early genes in rat cerebral cortex. Brain Res Mol Brain Res. 1991, 11(1):43-6. PMID: 1662744
47. Bing G, Notter MF, Hansen JT, Kellogg C, Kordower JH, Gash DM. Cografts of adrenal medulla with C6 glioma cells in rats with 6-hydroxydopamine-induced lesions. Neuroscience. 1990, 34(3):687-97. PMID: 1972269
48. Bing GY, Notter MF, Hansen JT, Gash DM. Comparison of adrenal medullary, carotid body and PC12 cell grafts in 6-OHDA lesioned rats. Brain Res Bull. 1988, 20(3):399-406. PMID: 2896533