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Lipopolysaccharide Induces Gliotoxicity in Hippocampal Astrocytes from Aged Rats: Insights About the Glioprotective Roles of Resveratrol

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Abstract

Astrocytes may undergo a functional remodeling with aging, acquiring a pro-inflammatory state. In line with this, resveratrol represents an interesting strategy for a healthier brain aging since it can improve glial functions. In the present study, we investigated the glioprotective role of resveratrol against lipopolysaccharide (LPS)-induced gliotoxicity in hippocampal aged astrocytes. Astrocyte cultures were obtained from aged rats (365 days old) and challenged in vitro with LPS in the presence of resveratrol. Cultured astrocytes from newborn rats were used as an age comparative for evaluating LPS gliotoxicity. In addition, aged rats were submitted to an acute systemic inflammation with LPS. Hippocampal astrocyte cultures were also obtained from these LPS-stimulated aged animals to further investigate the glioprotective effects of resveratrol in vitro. Overall, our results show that LPS induced a higher inflammatory response in aged astrocytes, compared to newborn astrocytes. Several inflammatory and gene expression alterations promoted by LPS in aged astrocyte cultures were similar in hippocampal tissue from aged animals submitted to in vivo LPS injection, corroborating our in vitro findings. Resveratrol, in turn, presented anti-inflammatory effects in aged astrocyte cultures, which were associated with downregulation of p21 and pro-inflammatory cytokines, Toll-like receptors (TLRs), and nuclear factor κB (NFκB). Resveratrol also improved astroglial functions. Upregulation of sirtuin 1 (SIRT1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) represent potential molecular mechanisms associated with resveratrol-mediated glioprotection. In summary, our data show that resveratrol can prime aged astrocytes against gliotoxic stimuli, contributing to a healthier brain aging.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

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References

  1. Partridge L, Deelen J, Slagboom PE (2018) Facing up to the global challenges of ageing. Nature 561:45–56. https://doi.org/10.1038/s41586-018-0457-8

    Article  CAS  PubMed  Google Scholar 

  2. López-Otín C, Blasco MA, Partridge L et al (2013) The Hallmarks of aging. Cell 153:1194–1217. https://doi.org/10.1016/j.cell.2013.05.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Shivarama Shetty M, Sajikumar S (2017) ‘Tagging’ along memories in aging: synaptic tagging and capture mechanisms in the aged hippocampus. Ageing Res Rev 35:22–35. https://doi.org/10.1016/j.arr.2016.12.008

    Article  PubMed  Google Scholar 

  4. Burke SN, Barnes CA (2006) Neural plasticity in the ageing brain. Nat Rev Neurosci 7:30–40. https://doi.org/10.1038/nrn1809

    Article  CAS  PubMed  Google Scholar 

  5. Rosenzweig ES, Barnes CA (2003) Impact of aging on hippocampal function: plasticity, network dynamics, and cognition. Prog Neurobiol 69:143–179. https://doi.org/10.1016/S0301-0082(02)00126-0

    Article  CAS  PubMed  Google Scholar 

  6. Valori CF, Guidotti G, Brambilla L, Rossi D (2019) Astrocytes: emerging therapeutic targets in neurological disorders. Trends Mol Med 25:750–759. https://doi.org/10.1016/j.molmed.2019.04.010

    Article  CAS  PubMed  Google Scholar 

  7. Mederos S, González-Arias C, Perea G (2018) Astrocyte–neuron networks: a multilane highway of signaling for homeostatic brain function. Front Synaptic Neurosci 10:45. https://doi.org/10.3389/fnsyn.2018.00045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32:421–431. https://doi.org/10.1016/j.tins.2009.05.001

    Article  CAS  PubMed  Google Scholar 

  9. Bolaños JP (2016) Bioenergetics and redox adaptations of astrocytes to neuronal activity. J Neurochem 139:115–125. https://doi.org/10.1111/jnc.13486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gonçalves C-A, Rodrigues L, Bobermin LD et al (2018) Glycolysis-Derived compounds from astrocytes that modulate synaptic communication. Front Neurosci 12:1035. https://doi.org/10.3389/fnins.2018.01035

    Article  PubMed  Google Scholar 

  11. Colombo E, Farina C (2016) Astrocytes: key regulators of neuroinflammation. Trends Immunol 37:608–620. https://doi.org/10.1016/j.it.2016.06.006

    Article  CAS  PubMed  Google Scholar 

  12. Jensen CJ, Massie A, De Keyser J (2013) Immune players in the CNS: the astrocyte. J Neuroimmune Pharmacol 8:824–839. https://doi.org/10.1007/s11481-013-9480-6

    Article  PubMed  Google Scholar 

  13. Bobermin LD, Roppa RHA, Quincozes-Santos A (2019) Adenosine receptors as a new target for resveratrol-mediated glioprotection. Biochim Biophys Acta Mol Basis Dis 1865:634–647. https://doi.org/10.1016/j.bbadis.2019.01.004

    Article  CAS  PubMed  Google Scholar 

  14. Gorina R, Font-Nieves M, Márquez-Kisinousky L et al (2011) Astrocyte TLR4 activation induces a proinflammatory environment through the interplay between MyD88-dependent NFκB signaling, MAPK, and Jak1/Stat1 pathways. Glia 59:242–255. https://doi.org/10.1002/glia.21094

    Article  PubMed  Google Scholar 

  15. Palmer AL, Ousman SS (2018) Astrocytes and aging Front Aging Neurosci 10:337. https://doi.org/10.3389/fnagi.2018.00337

    Article  CAS  PubMed  Google Scholar 

  16. Souza DG, Bellaver B, Souza DO, Quincozes-Santos A (2013) Characterization of adult rat astrocyte cultures. PLoS ONE 8:e60282. https://doi.org/10.1371/journal.pone.0060282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bellaver B, Souza DG, Souza DO, Quincozes-Santos A (2017) Hippocampal astrocyte cultures from adult and aged rats reproduce changes in glial functionality observed in the aging brain. Mol Neurobiol 54:2969–2985. https://doi.org/10.1007/s12035-016-9880-8

    Article  CAS  PubMed  Google Scholar 

  18. Santos CL, Roppa PHA, Truccolo P et al (2018) Age-dependent neurochemical remodeling of hypothalamic astrocytes. Mol Neurobiol 55:5565–5579. https://doi.org/10.1007/s12035-017-0786-x

    Article  CAS  PubMed  Google Scholar 

  19. Longoni A, Bellaver B, Bobermin LD et al (2018) Homocysteine induces glial reactivity in adult rat astrocyte cultures. Mol Neurobiol 55:1966–1976. https://doi.org/10.1007/s12035-017-0463-0

    Article  CAS  PubMed  Google Scholar 

  20. Santos CL, Bobermin LD, Souza DO, Quincozes-Santos A (2018) Leptin stimulates the release of pro-inflammatory cytokines in hypothalamic astrocyte cultures from adult and aged rats. Metab Brain Dis 33:2059–2063. https://doi.org/10.1007/s11011-018-0311-6

    Article  CAS  PubMed  Google Scholar 

  21. Wyss-Coray T (2016) Ageing, neurodegeneration and brain rejuvenation. Nature 539:180–186. https://doi.org/10.1038/nature20411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Davinelli S, Maes M, Corbi G et al (2016) Dietary phytochemicals and neuro-inflammaging: from mechanistic insights to translational challenges. Immun Ageing 13:16. https://doi.org/10.1186/s12979-016-0070-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Franceschi C (2007) Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr Rev 65:S173-176. https://doi.org/10.1111/j.1753-4887.2007.tb00358.x

    Article  PubMed  Google Scholar 

  24. Quincozes-Santos A, Gottfried C (2011) Resveratrol modulates astroglial functions: neuroprotective hypothesis: resveratrol modulates astroglial functions. Ann N Y Acad Sci 1215:72–78. https://doi.org/10.1111/j.1749-6632.2010.05857.x

    Article  CAS  PubMed  Google Scholar 

  25. Quincozes-Santos A, Bobermin LD, Latini A et al (2013) Resveratrol Protects C6 astrocyte cell line against hydrogen peroxide-induced oxidative stress through heme oxygenase 1. PLoS ONE 8:e64372. https://doi.org/10.1371/journal.pone.0064372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bellaver B, Bobermin LD, Souza DG et al (2016) Signaling mechanisms underlying the glioprotective effects of resveratrol against mitochondrial dysfunction. Biochim Biophys Acta BBA - Mol Basis Dis 1862:1827–1838. https://doi.org/10.1016/j.bbadis.2016.06.018

    Article  CAS  Google Scholar 

  27. Rosa PM, Martins LAM, Souza DO, Quincozes-Santos A (2018) Glioprotective effect of resveratrol: an emerging therapeutic role for oligodendroglial cells. Mol Neurobiol 55:2967–2978. https://doi.org/10.1007/s12035-017-0510-x

    Article  CAS  PubMed  Google Scholar 

  28. Bonkowski MS, Sinclair DA (2016) Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nat Rev Mol Cell Biol 17:679–690. https://doi.org/10.1038/nrm.2016.93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bhullar KS, Hubbard BP (2015) Lifespan and healthspan extension by resveratrol. Biochim Biophys Acta BBA - Mol Basis Dis 1852:1209–1218. https://doi.org/10.1016/j.bbadis.2015.01.012

    Article  CAS  Google Scholar 

  30. Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5:493–506. https://doi.org/10.1038/nrd2060

    Article  CAS  PubMed  Google Scholar 

  31. Price NL, Gomes AP, Ling AJY et al (2012) SIRT1 Is Required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab 15:675–690. https://doi.org/10.1016/j.cmet.2012.04.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hwang J, Yao H, Caito S et al (2013) Redox regulation of SIRT1 in inflammation and cellular senescence. Free Radic Biol Med 61:95–110. https://doi.org/10.1016/j.freeradbiomed.2013.03.015

    Article  CAS  PubMed  Google Scholar 

  33. Lee S-H, Lee J-H, Lee H-Y, Min K-J (2019) Sirtuin signaling in cellular senescence and aging. BMB Rep 52:24–34. https://doi.org/10.5483/BMBRep.2019.52.1.290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sarubbo F, Esteban S, Miralles A, Moranta D (2018) Effects of resveratrol and other polyphenols on Sirt1: relevance to brain function during aging.Curr Neuropharmacol 16https://doi.org/10.2174/1570159X15666170703113212

  35. Bellaver B, Souza DG, Bobermin LD et al (2015) Resveratrol Protects hippocampal astrocytes against lps-induced neurotoxicity through HO-1, p38 and erk pathways. Neurochem Res 40:1600–1608. https://doi.org/10.1007/s11064-015-1636-8

    Article  CAS  PubMed  Google Scholar 

  36. Bobermin LD, Quincozes-Santos A, Guerra MC et al (2012) Resveratrol prevents ammonia toxicity in astroglial cells. PLoS ONE 7:e52164. https://doi.org/10.1371/journal.pone.0052164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Allen EN, Potdar S, Tapias V et al (2018) Resveratrol and pinostilbene confer neuroprotection against aging-related deficits through an ERK1/2-dependent mechanism. J Nutr Biochem 54:77–86. https://doi.org/10.1016/j.jnutbio.2017.10.015

    Article  CAS  PubMed  Google Scholar 

  38. Bellaver B, Souza DG, Souza DO, Quincozes-Santos A (2014) Resveratrol increases antioxidant defenses and decreases proinflammatory cytokines in hippocampal astrocyte cultures from newborn, adult and aged Wistar rats. Toxicol Vitro Int J Publ Assoc BIBRA 28:479–484. https://doi.org/10.1016/j.tiv.2014.01.006

    Article  CAS  Google Scholar 

  39. Bobermin LD, Roppa RHA, Gonçalves C-A, Quincozes-Santos A (2020) ammonia-induced glial-inflammaging. Mol Neurobiol 57:3552–3567. https://doi.org/10.1007/s12035-020-01985-4

    Article  CAS  PubMed  Google Scholar 

  40. Guerra M, Tortorelli LS, Galland F et al (2011) Lipopolysaccharide modulates astrocytic S100B secretion: a study in cerebrospinal fluid and astrocyte cultures from rats. J Neuroinflammation 8:128. https://doi.org/10.1186/1742-2094-8-128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods San Diego Calif 25:402–408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  Google Scholar 

  42. Quincozes-Santos A, Nardin P, de Souza DF et al (2009) The janus face of resveratrol in astroglial cells. Neurotox Res 16:30–41. https://doi.org/10.1007/s12640-009-9042-0

    Article  CAS  PubMed  Google Scholar 

  43. Reers M, Smiley ST, Mottola-Hartshorn C et al (1995) Mitochondrial membrane potential monitored by JC-1 dye. Methods Enzymol 260:406–417. https://doi.org/10.1016/0076-6879(95)60154-6

    Article  CAS  PubMed  Google Scholar 

  44. Browne RW, Armstrong D (1998) Reduced glutathione and glutathione disulfide. free radical and antioxidant protocols. Humana Press, New Jersey, pp 347–352

    Chapter  Google Scholar 

  45. Seelig GF, Meister A (1985) Glutathione biosynthesis; gamma-glutamylcysteine synthetase from rat kidney. Methods Enzymol 113:379–390. https://doi.org/10.1016/s0076-6879(85)13050-8

    Article  CAS  PubMed  Google Scholar 

  46. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    Article  CAS  PubMed  Google Scholar 

  47. Cohen J, Torres C (2019) Astrocyte senescence: evidence and significance. Aging Cell 18:e12937. https://doi.org/10.1111/acel.12937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Clarke LE, Liddelow SA, Chakraborty C et al (2018) Normal aging induces A1-like astrocyte reactivity. Proc Natl Acad Sci 115:E1896–E1905. https://doi.org/10.1073/pnas.1800165115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Franceschi C, Garagnani P, Parini P et al (2018) Inflammaging: a new immune–metabolic viewpoint for age-related diseases. Nat Rev Endocrinol 14:576–590. https://doi.org/10.1038/s41574-018-0059-4

    Article  CAS  PubMed  Google Scholar 

  50. Calabrese V, Santoro A, Monti D et al (2018) Aging and Parkinson’s Disease: inflammaging, neuroinflammation and biological remodeling as key factors in pathogenesis. Free Radic Biol Med 115:80–91. https://doi.org/10.1016/j.freeradbiomed.2017.10.379

    Article  CAS  PubMed  Google Scholar 

  51. Souza DG, Bellaver B, Bobermin LD et al (2016) Anti-aging effects of guanosine in glial cells. Purinergic Signal 12:697–706. https://doi.org/10.1007/s11302-016-9533-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Souza DG, Bellaver B, Raupp GS et al (2015) Astrocytes from adult Wistar rats aged in vitro show changes in glial functions. Neurochem Int 90:93–97. https://doi.org/10.1016/j.neuint.2015.07.016

    Article  CAS  PubMed  Google Scholar 

  53. Wyse AT, Siebert C, Bobermin LD et al (2020) Changes in inflammatory response, redox status and Na+, K+-ATPase activity in primary astrocyte cultures from female wistar rats subject to ovariectomy. Neurotox Res 37:445–454. https://doi.org/10.1007/s12640-019-00128-5

    Article  CAS  PubMed  Google Scholar 

  54. Kodali M, Parihar VK, Hattiangady B et al (2015) Resveratrol prevents age-related memory and mood dysfunction with increased hippocampal neurogenesis and microvasculature and reduced glial activation. Sci Rep 5:8075. https://doi.org/10.1038/srep08075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lalo U, Pankratov Y (2021) Astrocytes as perspective targets of exercise- and caloric restriction-mimetics. Neurochem Res. https://doi.org/10.1007/s11064-021-03277-2

    Article  PubMed  PubMed Central  Google Scholar 

  56. Zhu X, Chen Z, Shen W et al (2021) Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention. Signal Transduct Target Ther 6:245. https://doi.org/10.1038/s41392-021-00646-9

    Article  PubMed  PubMed Central  Google Scholar 

  57. Ahmed A, Williams B, Hannigan G (2015) Transcriptional activation of inflammatory genes: mechanistic insight into selectivity and diversity. Biomolecules 5:3087–3111. https://doi.org/10.3390/biom5043087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bettio LEB, Rajendran L, Gil-Mohapel J (2017) The effects of aging in the hippocampus and cognitive decline. Neurosci Biobehav Rev 79:66–86. https://doi.org/10.1016/j.neubiorev.2017.04.030

    Article  PubMed  Google Scholar 

  59. Fan X, Wheatley EG, Villeda SA (2017) Mechanisms of hippocampal aging and the potential for rejuvenation. Annu Rev Neurosci 40:251–272. https://doi.org/10.1146/annurev-neuro-072116-031357

    Article  CAS  PubMed  Google Scholar 

  60. van Horssen J, van Schaik P, Witte M (2019) Inflammation and mitochondrial dysfunction: a vicious circle in neurodegenerative disorders? Neurosci Lett 710:132931. https://doi.org/10.1016/j.neulet.2017.06.050

    Article  CAS  PubMed  Google Scholar 

  61. Cobley JN, Fiorello ML, Bailey DM (2018) 13 reasons why the brain is susceptible to oxidative stress. Redox Biol 15:490–503. https://doi.org/10.1016/j.redox.2018.01.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. López-Navarro ME, Jarquín-Martínez M, Sánchez-Labastida LA et al (2020) Decoding aging: understanding the complex relationship among aging, free radicals, and GSH. Oxid Med Cell Longev 2020:1–11. https://doi.org/10.1155/2020/3970860

    Article  CAS  Google Scholar 

  63. Arús BA, Souza DG, Bellaver B et al (2017) Resveratrol modulates GSH system in C6 astroglial cells through heme oxygenase 1 pathway. Mol Cell Biochem 428:67–77. https://doi.org/10.1007/s11010-016-2917-5

    Article  CAS  PubMed  Google Scholar 

  64. Potier B, Billard J-M, Rivière S et al (2010) Reduction in glutamate uptake is associated with extrasynaptic NMDA and metabotropic glutamate receptor activation at the hippocampal CA1 synapse of aged rats: synaptic effects of reduced glutamate uptake in the aged rat hippocampus. Aging Cell 9:722–735. https://doi.org/10.1111/j.1474-9726.2010.00593.x

    Article  CAS  PubMed  Google Scholar 

  65. Todd AC, Hardingham GE (2020) The regulation of astrocytic glutamate transporters in health and neurodegenerative diseases. Int J Mol Sci 21:9607. https://doi.org/10.3390/ijms21249607

    Article  CAS  PubMed Central  Google Scholar 

  66. Barnes JR, Mukherjee B, Rogers BC et al (2020) The relationship between glutamate dynamics and activity-dependent synaptic plasticity. J Neurosci 40:2793–2807. https://doi.org/10.1523/JNEUROSCI.1655-19.2020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Zhang Y, Sloan SA, Clarke LE et al (2016) Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron 89:37–53. https://doi.org/10.1016/j.neuron.2015.11.013

    Article  CAS  PubMed  Google Scholar 

  68. Tian G, Lai L, Guo H et al (2007) Translational control of glial glutamate transporter EAAT2 expression. J Biol Chem 282:1727–1737. https://doi.org/10.1074/jbc.M609822200

    Article  CAS  PubMed  Google Scholar 

  69. Ryan RM, Ingram SL, Scimemi A (2021) Regulation of glutamate, GABA and dopamine transporter uptake, surface mobility and expression. Front Cell Neurosci 15:670346. https://doi.org/10.3389/fncel.2021.670346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Piao C, Ranaivo HR, Rusie A et al (2015) Thrombin decreases expression of the glutamate transporter GLAST and inhibits glutamate uptake in primary cortical astrocytes via the Rho kinase pathway. Exp Neurol 273:288–300. https://doi.org/10.1016/j.expneurol.2015.09.009

    Article  CAS  PubMed  Google Scholar 

  71. Miralles VJ, Martínez-López I, Zaragozá R et al (2001) Na+ dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) in primary astrocyte cultures: effect of oxidative stress. Brain Res 922:21–29. https://doi.org/10.1016/s0006-8993(01)03124-9

    Article  CAS  PubMed  Google Scholar 

  72. Hertz L (2003) Astrocytic amino acid metabolism under control conditions and during oxygen and/or glucose deprivation. Neurochem Res 28:243–258. https://doi.org/10.1023/A:1022377100379

    Article  CAS  PubMed  Google Scholar 

  73. Tong L, Balazs R, Soiampornkul R et al (2008) Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction. Neurobiol Aging 29:1380–1393. https://doi.org/10.1016/j.neurobiolaging.2007.02.027

    Article  CAS  PubMed  Google Scholar 

  74. Lima Giacobbo B, Doorduin J, Klein HC et al (2019) Brain-Derived neurotrophic factor in brain disorders: focus on neuroinflammation. Mol Neurobiol 56:3295–3312. https://doi.org/10.1007/s12035-018-1283-6

    Article  CAS  PubMed  Google Scholar 

  75. Budni J, Bellettini-Santos T, Mina F, et al (2015) The involvement of BDNF, NGF and GDNF in aging and Alzheimer’s disease. Aging Dis 6:331. https://doi.org/10.14336/AD.2015.0825

  76. Sakata Y, Zhuang H, Kwansa H et al (2010) Resveratrol protects against experimental stroke: putative neuroprotective role of heme oxygenase 1. Exp Neurol 224:325–329. https://doi.org/10.1016/j.expneurol.2010.03.032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Liddell J (2017) Are Astrocytes the predominant cell type for activation of nrf2 in Aging and neurodegeneration? Antioxidants 6:65. https://doi.org/10.3390/antiox6030065

    Article  CAS  PubMed Central  Google Scholar 

  78. Ahmed SMU, Luo L, Namani A et al (2017) Nrf2 signaling pathway: pivotal roles in inflammation. Biochim Biophys Acta BBA - Mol Basis Dis 1863:585–597. https://doi.org/10.1016/j.bbadis.2016.11.005

    Article  CAS  Google Scholar 

  79. Kauppinen A, Suuronen T, Ojala J et al (2013) Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal 25:1939–1948. https://doi.org/10.1016/j.cellsig.2013.06.007

    Article  CAS  PubMed  Google Scholar 

  80. Bellaver B, Dos Santos JP, Leffa DT et al (2018) Systemic inflammation as a driver of brain injury: the astrocyte as an emerging player. Mol Neurobiol 55:2685–2695. https://doi.org/10.1007/s12035-017-0526-2

    Article  CAS  PubMed  Google Scholar 

  81. Cian RE, López-Posadas R, Drago SR et al (2012) A Porphyra columbina hydrolysate upregulates IL-10 production in rat macrophages and lymphocytes through an NF-κB, and p38 and JNK dependent mechanism. Food Chem 134:1982–1990. https://doi.org/10.1016/j.foodchem.2012.03.134

    Article  CAS  PubMed  Google Scholar 

  82. Xu X, Guo Y, Zhao J et al (2017) Punicalagin, a PTP1B inhibitor, induces M2c phenotype polarization via up-regulation of HO-1 in murine macrophages. Free Radic Biol Med 110:408–420. https://doi.org/10.1016/j.freeradbiomed.2017.06.014

    Article  CAS  PubMed  Google Scholar 

  83. Rodgers KR, Lin Y, Langan TJ et al (2020) Innate Immune functions of astrocytes are dependent upon tumor necrosis factor-alpha. Sci Rep 10:7047. https://doi.org/10.1038/s41598-020-63766-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Villarreal A, Seoane R, González Torres A et al (2014) S100B protein activates a RAGE-dependent autocrine loop in astrocytes: implications for its role in the propagation of reactive gliosis. J Neurochem 131:190–205. https://doi.org/10.1111/jnc.12790

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Universidade Federal do Rio Grande do Sul and Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção (INCTEN/CNPq).

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Authors and Affiliations

  1. Programa de Pós-Graduação Em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil

    Larissa Daniele Bobermin, Rômulo Rodrigo de Souza Almeida, Angela T. S. Wyse, Carlos-Alberto Gonçalves & André Quincozes-Santos

  2. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul– UFRGS, Rua Ramiro Barcelos, 2600 – Anexo Bairro Santa Cecília, Porto Alegre, RS, Brazil

    Fernanda Becker Weber, Lara Scopel Medeiros, Lívia Medeiros, Angela T. S. Wyse, Carlos-Alberto Gonçalves & André Quincozes-Santos

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  1. Larissa Daniele Bobermin
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  2. Rômulo Rodrigo de Souza Almeida
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  7. Carlos-Alberto Gonçalves
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  8. André Quincozes-Santos
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Contributions

AQS and LDB conceptualized the study. LDB, RRSA, FBW, LSM, and LM performed the experiments. LDB and AQS performed statistical analysis and written the original draft of the manuscript. AQS, ATSW, and CAG provided resources and materials/chemicals. All authors revised, edited, and approved the manuscript.

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Correspondence to André Quincozes-Santos.

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All animal experiments were performed in accordance with the National Institute of Health (NIH) Guide for the Care and Use of Laboratory Animals and Brazilian Society for Neuroscience and Behavior recommendations for animal care. The experimental protocols were approved by the Federal University of Rio Grande do Sul Animal Care and Use Committee (process number: 21215).

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Figure S1.

Effects of HO-1 inhibitor on cytokine release in aged astrocytes. Primary hippocampal astrocyte cultures from aged rats were incubated with LPS (1 μg/ml) for 24 h in the presence or absence of resveratrol (10 μM) and HO-1 inhibitor ZnPP IX (10 μM). The extracellular levels of TNF-α (A), IL-1β (B), IL-6 (C), MCP-1 (D), and IL-10 (E) were evaluated. Data are presented as mean ± S.D. and differences among groups were statistically analyzed using one-way analysis of variance (ANOVA), followed by Tukey’s test (n = 6 independent cultures and, at least, duplicate of treatments). Values of P < 0.05 were considered significant. a refers to statistically significant differences from the control conditions; b refers to statistically significant differences from LPS challenge. RSV, resveratrol. (PNG 14239 kb)

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Figure S2.

Effects of HO-1 and p38 MAPK inhibitors on glutamate uptake in aged astrocytes. Primary hippocampal astrocyte cultures from aged rats were incubated with LPS (1 μg/ml) for 24 h in the presence or absence of resveratrol (10 μM) and HO-1 inhibitor ZnPP IX (10 μM) or p38 MAPK inhibitor SB203580 (10 μM), A and B, respectively. Data are presented as mean ± S.D. and differences among groups were statistically analyzed using one-way analysis of variance (ANOVA), followed by Tukey’s test (n = 6 independent cultures and, at least, duplicate of treatments). Values of P < 0.05 were considered significant. a refers to statistically significant differences from the control conditions; b refers to statistically significant differences from LPS challenge. RSV, resveratrol. (PNG 8928 kb)

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Bobermin, L.D., de Souza Almeida, R.R., Weber, F.B. et al. Lipopolysaccharide Induces Gliotoxicity in Hippocampal Astrocytes from Aged Rats: Insights About the Glioprotective Roles of Resveratrol. Mol Neurobiol 59, 1419–1439 (2022). https://doi.org/10.1007/s12035-021-02664-8

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