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Open Access 01-12-2018 | Research

Dual modulation on glial cells by tetrahydroxystilbene glucoside protects against dopamine neuronal loss

Published in: Journal of Neuroinflammation | Issue 1/2018

Abstract

Background

Microglia-mediated neuroinflammation is recognized to mainly contribute to the pathogenesis of Parkinson’s disease (PD). Tetrahydroxystilbene glucoside (TSG) has been proved to be beneficial for health with a great number of pharmacological properties. We examined the effects of TSG against dopamine (DA) neuronal loss towards development of a PD treatment strategy.

Methods

Substantia nigral stereotaxic single injection of lipopolysaccharide (LPS)-induced rat DA neuronal damage was employed to investigate TSG-produced neuroprotection. In addition, primary rat midbrain neuron-glia co-cultures were performed to explore the underlying mechanisms.

Results

Daily intraperitoneal injection of TSG for seven consecutive days significantly attenuated LPS-induced loss of DA neurons in the substantia nigra. In addition, glia-dependent mechanisms were responsible for TSG-mediated neuroprotection. First, TSG ameliorated microglia-mediated neuroinflammation and the subsequent production of various pro-inflammatory and neurotoxic factors. Second, astroglial neurotrophic factor neutralization weakened TSG-mediated neuroprotection, showing that TSG was protective in part via increasing astroglia-derived neurotrophic factor secretion.

Conclusions

TSG protects DA neurons against LPS-induced neurotoxicity through dual modulation on glial cells by attenuating microglia-mediated neuroinflammation and enhancing astroglia-derived neurotrophic effects. These findings might open new alternative avenues for PD treatment.

Tentillier N, Etzerodt A, Olesen MN, Rizalar FS, Jacobsen J, Bender D, et al. Anti-inflammatory modulation of microglia via CD163-targeted glucocorticoids protects dopaminergic neurons in the 6-OHDA Parkinson’s disease model. J Neurosci. 2016;36:9375–90.CrossRefPubMed

Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci. 2007;8:57–69.CrossRefPubMed

Gao HM, Hong JS. Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol. 2008;29:357–65.CrossRefPubMedPubMedCentral

Tsai HH, Li H, Fuentealba LC, Molofsky AV, Taveira-Marques R, Zhuang H, et al. Regional astrocyte allocation regulates CNS synaptogenesis and repair. Sci. 2012;337:358–62.CrossRef

Furman JL, Sama DM, Gant JC, Beckett TL, Murphy MP, Bachstetter AD, et al. Targeting astrocytes ameliorates neurologic changes in a mouse model of Alzheimer’s disease. J Neurosci. 2012;32:16129–40.CrossRefPubMedPubMedCentral

Cheng PL, Song AH, Wong YH, Wang S, Zhang X, Poo MM. Self-amplifying autocrine actions of BDNF in axon development. Proc Natl Acad Sci U S A. 2011;108:18430–5.CrossRefPubMedPubMedCentral

Sarhan M, Pawlowski SA, Barthas F, Yalcin I, Kaufling J, Dardente H, et al. BDNF parabrachio-amygdaloid pathway in morphine-induced analgesia. Int J Neuropsychopharmacol. 2013;16:1649–60.CrossRefPubMed

Zeng C, Xiao JH, Chang MJ, Wang JL. Beneficial effects of THSG on acetic acid-induced experimental colitis: involvement of upregulation of PPAR-γ and inhibition of the Nf-Κb inflammatory pathway. Mol. 2011;16:8552–68.CrossRef

Wang T, Gu J, Wu PF, Wang F, Xiong Z, Yang YJ, et al. Protection by tetrahydroxystilbene glucoside against cerebral ischemia: involvement of JNK, SIRT1, and NF-kappaB pathways and inhibition of intracellular ROS/RNS generation. Free Radic Biol Med. 2009;47:229–40.CrossRefPubMed

10.

Zhang F, Qian L, Flood PM, Shi JS, Hong JS, Gao HM. Inhibition of IkappaB kinase-beta protects dopamine neurons against lipopolysaccharide-induced neurotoxicity. J Pharmacol Exp Ther. 2010;333:822–33.CrossRefPubMedPubMedCentral

11.

Zhang F, Shi JS, Zhou H, Wilson B, Hong JS, Gao HM. Resveratrol protects dopamine neurons against LPS-induced neurotoxicity through its anti-inflammatory actions. Mol Pharmacol. 2010;78:466–77.CrossRefPubMedPubMedCentral

12.

Zhang W, Shin EJ, Wang T, Lee PH, Pang H, Wie MB, et al. 3-Hydroxymorphinan, a metabolite of dextromethorphan, protects nigrostriatal pathway against MPTP-elicited damage both in vivo and in vitro. FASEB J. 2006;20:2496–511.CrossRefPubMed

13.

Gao HM, Hong JS, Zhang W, Liu B. Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J Neurosci. 2002;22:782–90.CrossRefPubMed

14.

Lin F, Zhou Y, Shi W, Wang Y, Zhang Z, Zhang F. Tetrahydroxystilbene glucoside improves neurotrophic factors release in cultured astroglia. CNS Neurol Disord Drug Targets. 2016;15:514–9.CrossRefPubMed

15.

Liu B, Du L, Hong JS. Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation. J Pharmacol Exp Ther. 2000;293:607–17.PubMed

16.

Khuwaja G, Khan MM, Ishrat T, Ahmad A, Raza SS, Ashafaq M, et al. Neuroprotective effects of curcumin on 6-hydroxydopamine-induced Parkinsonism in rats: behavioral, neurochemical and immunohistochemical studies. Brain Res. 2011;1368:254–63.CrossRefPubMed

17.

Jackson-Lewis V, Smeyne RJ. MPTP and SNpc DA neuronal vulnerability: role of dopamine, superoxide and nitric oxide in neurotoxicity. Neurotox Res. 2005;7:193–202.CrossRefPubMed

18.

Vivekanantham S, Shah S, Dewji R, Dewji A, Khatri C, Ologunde R. Neuroinflammation in Parkinson’s disease: role in neurodegeneration and tissue repair. Int J Neurosci. 2015;125:717–25.CrossRefPubMed

19.

Lee DS, Jeong GS. Butein provides neuroprotective and anti-neuroinflammatory effects through Nrf2/ARE-dependent haem oxygenase 1 expression by activating the PI3K/Akt pathway. Br J Pharmacol. 2016;173:2894–909.CrossRefPubMedPubMedCentral

20.

Chen SH, Oyarzabal EA, Hong JS. Critical role of the Mac1/NOX2 pathway in mediating reactive microgliosis-generated chronic neuroinflammation and progressive neurodegeneration. Curr Opin Pharmacol. 2016;26:54–60.CrossRefPubMed

21.

Leem E, Jeong KH, Won SY, Shin WH, Kim SR. Prothrombin kringle-2: a potential inflammatory pathogen in the parkinsonian dopaminergic system. Exp Neurobiol. 2016;25:147–55.CrossRefPubMedPubMedCentral

22.

Zhang F, Wang YY, Yang J, Lu YF, Liu J, Shi JS. Tetrahydroxystilbene glucoside attenuates neuroinflammation through the inhibition of microglia activation. Oxidative Med Cell Longev. 2013;2013:680545.

23.

Xie Y, Chen Y. microRNAs: emerging targets regulating oxidative stress in the models of Parkinson’s disease. Front Neurosci. 2016;10:298.CrossRefPubMedPubMedCentral

24.

Gao HM, Zhang F, Zhou H, Kam W, Wilson B, Hong JS. Neuroinflammation and α-synuclein dysfunction potentiate each other, driving chronic progression of neurodegeneration in a mouse model of Parkinson’s disease. Environ Health Perspect. 2011;119:807–14.CrossRefPubMedPubMedCentral

25.

Ebadi M, Sharma SK, Ghafourifar P, Brown-Borg H, El Refaey H. Peroxynitrite in the pathogenesis of Parkinson’s disease and the neuroprotective role of metallothioneins. Methods Enzymol. 2005;396:276–98.CrossRefPubMed

26.

Wang Q, Qian L, Chen SH, Chu CH, Wilson B, Oyarzabal E, et al. Post-treatment with an ultra-low dose of NADPH oxidase inhibitor diphenyleneiodonium attenuates disease progression in multiple Parkinson's disease models. Brain. 2015;138:1247–62.CrossRefPubMedPubMedCentral

27.

Gao HM, Zhou H, Zhang F, Wilson BC, Kam W, Hong JS. HMGB1 acts on microglia Mac1 to mediate chronic neuroinflammation that drives progressive neurodegeneration. J Neurosci. 2011;31:1081–92.CrossRefPubMedPubMedCentral

28.

Bhatia HS, Baron J, Hagl S, Eckert GP, Fiebich BL. Rice bran derivatives alleviate microglia activation: possible involvement of MAPK pathway. J Neuroinflammation. 2016;13:148.CrossRefPubMedPubMedCentral

29.

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;192:89–98.CrossRefPubMed

30.

Ramanan S, Kooshki M, Zhao W, Hsu FC, Robbins ME. PPARalpha ligands inhibit radiation-induced microglial inflammatory responses by negatively regulating NF-kappaB and AP-1 pathways. Free Radic Biol Med. 2008;45:1695–704.CrossRefPubMedPubMedCentral

31.

Youn GS, Lee KW, Choi SY, Park J. Overexpression of HDAC6 induces pro-inflammatory responses by regulating ROS-MAPK- NF-κB/AP-1 signaling pathways in macrophages. Free Radic Biol Med. 2016;97:14–23.CrossRefPubMed

32.

Han CL, Ge M, Liu YP, Zhao XM, Wang KL, Chen N, et al. LncRNA H19 contributes to hippocampal glial cell activation via JAK/STAT signaling in a rat model of temporal lobe epilepsy. J Neuroinflammation. 2018;15(1):103.CrossRefPubMedPubMedCentral

33.

Norden DM, Trojanowski PJ, Villanueva E, Navarro E, Godbout JP. Sequential activation of microglia and astrocyte cytokine expression precedes increased Iba-1 or GFAP immunoreactivity following systemic immune challenge. Glia. 2016;64(2):300–16.CrossRefPubMed

34.

Wadhwa M, Chauhan G, Roy K, Sahu S, Deep S, Jain V, et al. Caffeine and modafinil ameliorate the neuroinflammation and anxious behavior in rats during sleep deprivation by inhibiting the microglia activation. Front Cell Neurosci. 2018;12:49.CrossRefPubMedPubMedCentral

35.

Xu J, Zhang X, Qian Q, Wang Y, Dong H, Li N, et al. Histamine upregulates the expression of histamine receptors and increases the neuroprotective effect of astrocytes. J Neuroinflammation. 2018;15(1):41.CrossRefPubMedPubMedCentral

36.

Sullivan AM, Toulouse A. Neurotrophic factors for the treatment of Parkinson’s disease. Cytokine Growth Factor Rev. 2011;22:157–65.CrossRefPubMed

37.

Schindowski K, Belarbi K, Buee L. Neurotrophic factors in Alzheimer’s disease: role of axonal transport. Genes Brain Behav. 2008;7:43–56.CrossRefPubMedPubMedCentral

38.

Longo FM, Massa SM. Small-molecule modulation of neurotrophin receptors: a strategy for the treatment of neurological disease. Nat Rev Drug Discov. 2013;12:507–25.CrossRefPubMed

39.

Yang WH, Yang C, Xue YQ, Lu T, Reiser J, Zhao LR, et al. Regulated expression of lentivirus-mediated GDNF in human bone marrow-derived mesenchymal stem cells and its neuroprotection on dopaminergic cells in vitro. PLoS One. 2013;8:e64389.CrossRefPubMedPubMedCentral

40.

Gill SS, Patel NK, Hotton GR, O’Sullivan K, McCarter R, Bunnage M, et al. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med. 2003;9:589–95.CrossRefPubMed

41.

Jang SW, Liu X, Yepes M, Shepherd KR, Miller GW, Liu Y, et al. A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone. Proc Natl Acad Sci U S A. 2010;107:2687–92.CrossRefPubMedPubMedCentral

42.

Rothman SM, Mattson MP. Activity-dependent, stress-responsive BDNF signaling and the quest for optimal brain health and resilience throughout the lifespan. Neurosci. 2013;239:228–40.CrossRef

43.

Divito CB, Steece-Collier K, Case DT, Williams SP, Stancati JA, Zhi L, et al. Loss of VGLUT3 produces circadian-dependent hyperdopaminergia and ameliorates motor dysfunction and l-Dopa-mediated dyskinesias in a model of Parkinson’s disease. J Neurosci. 2015;35:14983–99.CrossRefPubMedPubMedCentral

44.

Horng LY, Hsu PL, Chen LW, Tseng WZ, Hsu KT, Wu CL, et al. Activating mitochondrial function and haemoglobin expression with EH-201, an inducer of erythropoietin in neuronal cells, reverses memory impairment. Br J Pharmacol. 2015;172:4741–56.CrossRefPubMedPubMedCentral

45.

46.

Huang C, Wang Y, Wang J, Yao W, Chen X, Zhang W. TSG (2,3,4′, 5-tetrahydroxystilbene 2-O-β-D-glucoside) suppresses induction of pro-inflammatory factors by attenuating the binding activity of nuclear factor-κB in microglia. J Neuroinflammation. 2013;10:129.CrossRefPubMedPubMedCentral

47.

Luo HB, Yang JX, Shi XD, Fu XF, Yang QD. Tetrahydroxy stilbene glucoside reduces the cognitive impairment and overexpression of amyloid precursor protein induced by aluminum exposure. Neurosci Bull. 2009;25(6):391–6.CrossRefPubMedPubMedCentral

48.

Ling S, Xu JW. Biological activities of 2,3,5,4’-tetrahydroxystilbene-2-O-β-D- glucoside in antiaging and antiaging-related disease treatments. Oxidative Med Cell Longev. 2016;2016:4973239.

Title: Dual modulation on glial cells by tetrahydroxystilbene glucoside protects against dopamine neuronal loss
Publication date: 01-12-2018
Published in: Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-018-1194-5

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Dual modulation on glial cells by tetrahydroxystilbene glucoside protects against dopamine neuronal loss

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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