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Hippocampal Astrocyte Cultures from Adult and Aged Rats Reproduce Changes in Glial Functionality Observed in the Aging Brain

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Abstract

Astrocytes are dynamic cells that maintain brain homeostasis, regulate neurotransmitter systems, and process synaptic information, energy metabolism, antioxidant defenses, and inflammatory response. Aging is a biological process that is closely associated with hippocampal astrocyte dysfunction. In this sense, we demonstrated that hippocampal astrocytes from adult and aged Wistar rats reproduce the glial functionality alterations observed in aging by evaluating several senescence, glutamatergic, oxidative and inflammatory parameters commonly associated with the aging process. Here, we show that the p21 senescence-associated gene and classical astrocyte markers, such as glial fibrillary acidic protein (GFAP), vimentin, and actin, changed their expressions in adult and aged astrocytes. Age-dependent changes were also observed in glutamate transporters (glutamate aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1)) and glutamine synthetase immunolabeling and activity. Additionally, according to in vivo aging, astrocytes from adult and aged rats showed an increase in oxidative/nitrosative stress with mitochondrial dysfunction, an increase in RNA oxidation, NADPH oxidase (NOX) activity, superoxide levels, and inducible nitric oxide synthase (iNOS) expression levels. Changes in antioxidant defenses were also observed. Hippocampal astrocytes also displayed age-dependent inflammatory response with augmentation of proinflammatory cytokine levels, such as TNF-α, IL-1β, IL-6, IL-18, and messenger RNA (mRNA) levels of cyclo-oxygenase 2 (COX-2). Furthermore, these cells secrete neurotrophic factors, including glia-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), S100 calcium-binding protein B (S100B) protein, and transforming growth factor-β (TGF-β), which changed in an age-dependent manner. Classical signaling pathways associated with aging, such as nuclear factor erythroid-derived 2-like 2 (Nrf2), nuclear factor kappa B (NFκB), heme oxygenase-1 (HO-1), and p38 mitogen-activated protein kinase (MAPK), were also changed in adult and aged astrocytes and are probably related to the changes observed in senescence marker, glutamatergic metabolism, mitochondrial dysfunction, oxidative/nitrosative stress, antioxidant defenses, inflammatory response, and trophic factors release. Together, our results reinforce the role of hippocampal astrocytes as a target for understanding the mechanisms involved in aging and provide an innovative tool for studies of astrocyte roles in physiological and pathological aging brain.

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References

  1. Farina C, Aloisi F, Meinl E (2007) Astrocytes are active players in cerebral innate immunity. Trends Immunol 28(3):138–145. doi:10.1016/j.it.2007.01.005

    Article  CAS  PubMed  Google Scholar 

  2. Hartline DK (2011) The evolutionary origins of glia. Glia 59(9):1215–1236. doi:10.1002/glia.21149

    Article  PubMed  Google Scholar 

  3. Kettenmann H, Verkhratsky A (2008) Neuroglia: the 150 years after. Trends Neurosci 31(12):653–659. doi:10.1016/j.tins.2008.09.003

    Article  CAS  PubMed  Google Scholar 

  4. Maragakis NJ, Rothstein JD (2006) Mechanisms of disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol 2(12):679–689. doi:10.1038/ncpneuro0355

    Article  CAS  PubMed  Google Scholar 

  5. Wang DD, Bordey A (2008) The astrocyte odyssey. Prog Neurobiol 86(4):342–367. doi:10.1016/j.pneurobio.2008.09.015

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Clarke LE, Barres BA (2013) Emerging roles of astrocytes in neural circuit development. Nat Rev Neurosci 14(5):311–321. doi:10.1038/nrn3484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Markiewicz I, Lukomska B (2006) The role of astrocytes in the physiology and pathology of the central nervous system. Acta Neurobiol Exp (Wars) 66(4):343–358

    Google Scholar 

  8. Donato R (2003) Intracellular and extracellular roles of S100 proteins. Microsc Res Tech 60(6):540–551. doi:10.1002/jemt.10296

    Article  CAS  PubMed  Google Scholar 

  9. Rodriguez-Arellano JJ, Parpura V, Zorec R, Verkhratsky A (2015) Astrocytes in physiological aging and Alzheimer’s disease. Neuroscience. doi:10.1016/j.neuroscience.2015.01.007

    PubMed  Google Scholar 

  10. Alarcon-Aguilar A, Luna-Lopez A, Ventura-Gallegos JL, Lazzarini R, Galvan-Arzate S, Gonzalez-Puertos VY, Moran J, Santamaria A et al (2014) Primary cultured astrocytes from old rats are capable to activate the Nrf2 response against MPP+ toxicity after tBHQ pretreatment. Neurobiol Aging 35(8):1901–1912. doi:10.1016/j.neurobiolaging.2014.01.143

    Article  CAS  PubMed  Google Scholar 

  11. Jiang T, Cadenas E (2014) Astrocytic metabolic and inflammatory changes as a function of age. Aging Cell 13(6):1059–1067. doi:10.1111/acel.12268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Miller DB, O’Callaghan JP (2005) Aging, stress and the hippocampus. Ageing Res Rev 4(2):123–140. doi:10.1016/j.arr.2005.03.002

    Article  CAS  PubMed  Google Scholar 

  13. Niccoli T, Partridge L (2012) Ageing as a risk factor for disease. Curr Biol 22(17):R741–R752. doi:10.1016/j.cub.2012.07.024

    Article  CAS  PubMed  Google Scholar 

  14. Gorina R, Font-Nieves M, Marquez-Kisinousky L, Santalucia T, Planas AM (2011) Astrocyte TLR4 activation induces a proinflammatory environment through the interplay between MyD88-dependent NFkappaB signaling, MAPK, and Jak1/Stat1 pathways. Glia 59(2):242–255. doi:10.1002/glia.21094

    Article  PubMed  Google Scholar 

  15. Vargas MR, Johnson JA (2009) The Nrf2-ARE cytoprotective pathway in astrocytes. Expert Rev Mol Med 11:e17. doi:10.1017/S1462399409001094

    Article  PubMed  Google Scholar 

  16. Gorg B, Karababa A, Shafigullina A, Bidmon HJ, Haussinger D (2015) Ammonia-induced senescence in cultured rat astrocytes and in human cerebral cortex in hepatic encephalopathy. Glia 63(1):37–50. doi:10.1002/glia.22731

    Article  PubMed  Google Scholar 

  17. Wakabayashi N, Slocum SL, Skoko JJ, Shin S, Kensler TW (2010) When NRF2 talks, who’s listening? Antioxid Redox Signal. doi:10.1089/ars.2010.3216

    Google Scholar 

  18. Orre M, Kamphuis W, Osborn LM, Melief J, Kooijman L, Huitinga I, Klooster J, Bossers K et al (2014) Acute isolation and transcriptome characterization of cortical astrocytes and microglia from young and aged mice. Neurobiol Aging 35(1):1–14. doi:10.1016/j.neurobiolaging.2013.07.008

    Article  CAS  PubMed  Google Scholar 

  19. Rodriguez JJ, Yeh CY, Terzieva S, Olabarria M, Kulijewicz-Nawrot M, Verkhratsky A (2014) Complex and region-specific changes in astroglial markers in the aging brain. Neurobiol Aging 35(1):15–23. doi:10.1016/j.neurobiolaging.2013.07.002

    Article  CAS  PubMed  Google Scholar 

  20. Rodrigues L, Biasibetti R, Swarowsky A, Leite MC, Quincozes-Santos A, Quilfeldt JA, Achaval M, Goncalves CA (2009) Hippocampal alterations in rats submitted to streptozotocin-induced dementia model are prevented by aminoguanidine. J Alzheimers Dis 17(1):193–202. doi:10.3233/JAD-2009-1034

    Article  CAS  PubMed  Google Scholar 

  21. Bellaver B, Souza DG, Souza DO, Quincozes-Santos A (2014) Resveratrol increases antioxidant defenses and deceases proinflammatory cytokines in hippocampal astocyte cultures from newborn, adult and aged Wistar rats. Toxicol in Vitro 28:479–484. doi:10.1016/j.tiv.2014.01.006

    Article  CAS  PubMed  Google Scholar 

  22. Souza DG, Bellaver B, Souza DO, Quincozes-Santos A (2013) Characterization of adult rat astrocyte cutures. PLoS One 8:E60282. doi:10.1371/journal.pone.0060282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 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 25(4):402–408. doi:10.1006/meth.2001.1262

    Article  CAS  PubMed  Google Scholar 

  24. Bellaver B, Souza DG, Bobermin LD, Goncalves CA, Souza DO, Quincozes-Santos A (2015) Guanosine inhibits LPS-induced pro-inflammatory response and oxidative stress in hippocampal astrocytes through the heme oxygenase-1 pathway. Purinergic Signal. doi:10.1007/s11302-015-9475-2

    PubMed  PubMed Central  Google Scholar 

  25. Quincozes-Santos A, Bobermin LD, Souza DG, Bellaver B, Goncalves CA, Souza DO (2014) Guanosine protects C6 astroglial cells against azide-induced oxidative damage: a putative role of heme oxygenase 1. J Neurochem 130(1):61–74. doi:10.1111/jnc.12694

    Article  CAS  PubMed  Google Scholar 

  26. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    CAS  PubMed  Google Scholar 

  27. Benarroch EE (2010) Glutamate transporters: diversity, function, and involvement in neurologic disease. Neurology 74(3):259–264. doi:10.1212/WNL.0b013e3181cc89e3

    Article  PubMed  Google Scholar 

  28. Brennan AM, Suh SW, Won SJ, Narasimhan P, Kauppinen TM, Lee H, Edling Y, Chan PH et al (2009) NADPH oxidase is the primary source of superoxide induced by NMDA receptor activation. Nat Neurosci 12(7):857–863. doi:10.1038/nn.2334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lee M, Cho T, Jantaratnotai N, Wang YT, McGeer E, McGeer PL (2010) Depletion of GSH in glial cells induces neurotoxicity: relevance to aging and degenerative neurological diseases. FASEB J 24(7):2533–2545. doi:10.1096/fj.09-149997

    Article  CAS  PubMed  Google Scholar 

  30. Heneka MT, Kummer MP, Latz E (2014) Innate immune activation in neurodegenerative disease. Nat Rev Immunol 14(7):463–477. doi:10.1038/nri3705

    Article  CAS  PubMed  Google Scholar 

  31. Kohman RA, Rhodes JS (2013) Neurogenesis, inflammation and behavior. Brain Behav Immun 27(1):22–32. doi:10.1016/j.bbi.2012.09.003

    Article  CAS  PubMed  Google Scholar 

  32. Yankner BA, Lu T, Loerch P (2008) The aging brain. Annu Rev Pathol 3:41–66. doi:10.1146/annurev.pathmechdis.2.010506.092044

    Article  CAS  PubMed  Google Scholar 

  33. Bhat R, Crowe EP, Bitto A, Moh M, Katsetos CD, Garcia FU, Johnson FB, Trojanowski JQ et al (2012) Astrocyte senescence as a component of Alzheimer’s disease. PLoS One 7(9):e45069. doi:10.1371/journal.pone.0045069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kawano H, Katsurabayashi S, Kakazu Y, Yamashita Y, Kubo N, Kubo M, Okuda H, Takasaki K et al (2012) Long-term culture of astrocytes attenuates the readily releasable pool of synaptic vesicles. PLoS One 7(10):e48034. doi:10.1371/journal.pone.0048034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Desclaux M, Teigell M, Amar L, Vogel R, Gimenez YRM, Privat A, Mallet J (2009) A novel and efficient gene transfer strategy reduces glial reactivity and improves neuronal survival and axonal growth in vitro. PLoS One 4(7):e6227. doi:10.1371/journal.pone.0006227

    Article  PubMed  PubMed Central  Google Scholar 

  36. Menet V, Gimenez y Ribotta M, Chauvet N, Drian MJ, Lannoy J, Colucci-Guyon E, Privat A (2001) Inactivation of the glial fibrillary acidic protein gene, but not that of vimentin, improves neuronal survival and neurite growth by modifying adhesion molecule expression. J Neurosci 21(16):6147–6158

    CAS  PubMed  Google Scholar 

  37. Pertusa M, Garcia-Matas S, Rodriguez-Farre E, Sanfeliu C, Cristofol R (2007) Astrocytes aged in vitro show a decreased neuroprotective capacity. J Neurochem 101(3):794–805. doi:10.1111/j.1471-4159.2006.04369.x

    Article  CAS  PubMed  Google Scholar 

  38. Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65(1):1–105. doi:10.1016/S0301-0082(00)00067-8

    Article  CAS  PubMed  Google Scholar 

  39. Ghosh M, Yang Y, Rothstein JD, Robinson MB (2011) Nuclear factor-kappaB contributes to neuron-dependent induction of glutamate transporter-1 expression in astrocytes. J Neurosci 31(25):9159–9169. doi:10.1523/jneurosci.0302-11.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Benediktsson AM, Marrs GS, Tu JC, Worley PF, Rothstein JD, Bergles DE, Dailey ME (2012) Neuronal activity regulates glutamate transporter dynamics in developing astrocytes. Glia 60(2):175–188. doi:10.1002/glia.21249

    Article  PubMed  Google Scholar 

  41. Anderson CM, Swanson RA (2000) Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32(1):1–14. doi:10.1002/1098-1136(200010)32:1<1::AID-GLIA10>3.0.CO;2-W

    Article  CAS  PubMed  Google Scholar 

  42. Schallier A, Smolders I, Van Dam D, Loyens E, De Deyn PP, Michotte A, Michotte Y, Massie A (2011) Region- and age-specific changes in glutamate transport in the AbetaPP23 mouse model for Alzheimer’s disease. J Alzheimers Dis 24(2):287–300. doi:10.3233/JAD-2011-101005

    CAS  PubMed  Google Scholar 

  43. Belanger M, Allaman I, Magistretti PJ (2011) Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 14(6):724–738. doi:10.1016/j.cmet.2011.08.016

    Article  CAS  PubMed  Google Scholar 

  44. Hertz L, Zielke HR (2004) Astrocytic control of glutamatergic activity: astrocytes as stars of the show. Trends Neurosci 27(12):735–743. doi:10.1016/j.tins.2004.10.008

    Article  CAS  PubMed  Google Scholar 

  45. Johnson JA, Johnson DA, Kraft AD, Calkins MJ, Jakel RJ, Vargas MR, Chen PC (2008) The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci 1147:61–69. doi:10.1196/annals.1427.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Dinkova-Kostova AT, Abramov AY (2015) The emerging role of Nrf2 in mitochondrial function. Free Radic Biol Med. doi:10.1016/j.freeradbiomed.2015.04.036

    Google Scholar 

  47. Motohashi H, Yamamoto M (2004) Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med 10(11):549–557. doi:10.1016/j.molmed.2004.09.003

    Article  CAS  PubMed  Google Scholar 

  48. Kovac S, Angelova PR, Holmstrom KM, Zhang Y, Dinkova-Kostova AT, Abramov AY (2015) Nrf2 regulates ROS production by mitochondria and NADPH oxidase. Biochim Biophys Acta 1850(4):794–801. doi:10.1016/j.bbagen.2014.11.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Volonte D, Liu Z, Musille PM, Stoppani E, Wakabayashi N, Di YP, Lisanti MP, Kensler TW et al (2013) Inhibition of nuclear factor-erythroid 2-related factor (Nrf2) by caveolin-1 promotes stress-induced premature senescence. Mol Biol Cell 24(12):1852–1862. doi:10.1091/mbc.E12-09-0666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mattson MP, Camandola S (2001) NF-kappaB in neuronal plasticity and neurodegenerative disorders. J Clin Invest 107(3):247–254. doi:10.1172/jci11916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ye B, Shen H, Zhang J, Zhu YG, Ransom BR, Chen XC, Ye ZC (2015) Dual pathways mediate beta-amyloid stimulated glutathione release from astrocytes. Glia 63(12):2208–2219. doi:10.1002/glia.22886

    Article  PubMed  Google Scholar 

  52. Webster SJ, Van Eldik LJ, Watterson DM (2015) Closed head injury in an age-related Alzheimer mouse model leads to an altered neuroinflammatory response and persistent cognitive impairment. J Neurosci 35(16):6554–6569. doi:10.1523/jneurosci.0291-15.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Suh SW, Shin BS, Ma H, Van Hoecke M, Brennan AM, Yenari MA, Swanson RA (2008) Glucose and NADPH oxidase drive neuronal superoxide formation in stroke. Ann Neurol 64(6):654–663. doi:10.1002/ana.21511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Suh SW, Hamby AM, Gum ET, Shin BS, Won SJ, Sheline CT, Chan PH, Swanson RA (2008) Sequential release of nitric oxide, zinc, and superoxide in hypoglycemic neuronal death. J Cereb Blood Flow Metab 28(10):1697–1706. doi:10.1038/jcbfm.2008.61

    Article  CAS  PubMed  Google Scholar 

  55. Gorg B, Qvartskhava N, Keitel V, Bidmon HJ, Selbach O, Schliess F, Haussinger D (2008) Ammonia induces RNA oxidation in cultured astrocytes and brain in vivo. Hepatology 48(2):567–579. doi:10.1002/hep.22345

    Article  PubMed  Google Scholar 

  56. Nunomura A, Hofer T, Moreira PI, Castellani RJ, Smith MA, Perry G (2009) RNA oxidation in Alzheimer disease and related neurodegenerative disorders. Acta Neuropathol 118(1):151–166. doi:10.1007/s00401-009-0508-1

    Article  CAS  PubMed  Google Scholar 

  57. Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82(1):47–95. doi:10.1152/physrev.00018.2001

    Article  CAS  PubMed  Google Scholar 

  58. Stewart VC, Stone R, Gegg ME, Sharpe MA, Hurst RD, Clark JB, Heales SJ (2002) Preservation of extracellular glutathione by an astrocyte derived factor with properties comparable to extracellular superoxide dismutase. J Neurochem 83(4):984–991. doi:10.1046/j.1471-4159.2002.01216.x

    Article  CAS  PubMed  Google Scholar 

  59. Trotti D, Danbolt NC, Volterra A (1998) Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration? Trends Pharmacol Sci 19(8):328–334. doi:10.1016/S0165-6147(98)01230-9

    Article  CAS  PubMed  Google Scholar 

  60. Liddell JR, Robinson SR, Dringen R, Bishop GM (2010) Astrocytes retain their antioxidant capacity into advanced old age. Glia 58(12):1500–1509. doi:10.1002/glia.21024

    PubMed  Google Scholar 

  61. Tanabe K, Kozawa O, Iida H (2011) Midazolam suppresses interleukin-1beta-induced interleukin-6 release from rat glial cells. J Neuroinflammation 8:68. doi:10.1186/1742-2094-8-68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. de Rivero Vaccari JP, Dietrich WD, Keane RW (2014) Activation and regulation of cellular inflammasomes: gaps in our knowledge for central nervous system injury. J Cereb Blood Flow Metab 34(3):369–375. doi:10.1038/jcbfm.2013.227

    Article  PubMed  PubMed Central  Google Scholar 

  63. Bossu P, Ciaramella A, Salani F, Vanni D, Palladino I, Caltagirone C, Scapigliati G (2010) Interleukin-18, from neuroinflammation to Alzheimer’s disease. Curr Pharm Des 16(38):4213–4224. doi:10.2174/138161210794519147

    Article  CAS  PubMed  Google Scholar 

  64. Xie Z, Morgan TE, Rozovsky I, Finch CE (2003) Aging and glial responses to lipopolysaccharide in vitro: greater induction of IL-1 and IL-6, but smaller induction of neurotoxicity. Exp Neurol 182(1):135–141. doi:10.1016/S0014-4886(03)00057-8

    Article  CAS  PubMed  Google Scholar 

  65. Tukhovskaya EA, Turovsky EA, Turovskaya MV, Levin SG, Murashev AN, Zinchenko VP, Godukhin OV (2014) Anti-inflammatory cytokine interleukin-10 increases resistance to brain ischemia through modulation of ischemia-induced intracellular Ca(2)(+) response. Neurosci Lett 571:55–60. doi:10.1016/j.neulet.2014.04.046

    Article  CAS  PubMed  Google Scholar 

  66. Sokolova A, Hill MD, Rahimi F, Warden LA, Halliday GM, Shepherd CE (2009) Monocyte chemoattractant protein-1 plays a dominant role in the chronic inflammation observed in Alzheimer’s disease. Brain Pathol 19(3):392–398. doi:10.1111/j.1750-3639.2008.00188.x

    Article  CAS  PubMed  Google Scholar 

  67. Kerschensteiner M, Meinl E, Hohlfeld R (2009) Neuro-immune crosstalk in CNS diseases. Neuroscience 158(3):1122–1132. doi:10.1016/j.neuroscience.2008.09.009

    Article  CAS  PubMed  Google Scholar 

  68. Bianchi R, Giambanco I, Donato R (2008) S100B/RAGE-dependent activation of microglia via NF-kappaB and AP-1 Co-regulation of COX-2 expression by S100B, IL-1beta and TNF-alpha. Neurobiol Aging 31(4):665–677. doi:10.1016/j.neurobiolaging.2008.05.017

    Article  PubMed  Google Scholar 

  69. Quesseveur G, David DJ, Gaillard MC, Pla P, Wu MV, Nguyen HT, Nicolas V, Auregan G et al (2013) BDNF overexpression in mouse hippocampal astrocytes promotes local neurogenesis and elicits anxiolytic-like activities. Translat Psychiatry 3:e253. doi:10.1038/tp.2013.30

    Article  CAS  Google Scholar 

  70. Chen Y, Ai Y, Slevin JR, Maley BE, Gash DM (2005) Progenitor proliferation in the adult hippocampus and substantia nigra induced by glial cell line-derived neurotrophic factor. Exp Neurol 196(1):87–95. doi:10.1016/j.expneurol.2005.07.010

    Article  CAS  PubMed  Google Scholar 

  71. Kleindienst A, McGinn MJ, Harvey HB, Colello RJ, Hamm RJ, Bullock MR (2005) Enhanced hippocampal neurogenesis by intraventricular S100B infusion is associated with improved cognitive recovery after traumatic brain injury. J Neurotrauma 22(6):645–655. doi:10.1089/neu.2005.22.645

    Article  PubMed  Google Scholar 

  72. Davila D, Thibault K, Fiacco TA, Agulhon C (2013) Recent molecular approaches to understanding astrocyte function in vivo. Front Cell Neurosci 7:272. doi:10.3389/fncel.2013.00272

    Article  PubMed  PubMed Central  Google Scholar 

  73. Hung SY, Liou HC, Fu WM (2010) The mechanism of heme oxygenase-1 action involved in the enhancement of neurotrophic factor expression. Neuropharmacology 58(2):321–329. doi:10.1016/j.neuropharm.2009.11.003

    Article  CAS  PubMed  Google Scholar 

  74. Mori T, Koyama N, Arendash GW, Horikoshi-Sakuraba Y, Tan J, Town T (2010) Overexpression of human S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer’s disease. Glia 58(3):300–314. doi:10.1002/glia.20924

    PubMed  PubMed Central  Google Scholar 

  75. Donato R, Sorci G, Riuzzi F, Arcuri C, Bianchi R, Brozzi F, Tubaro C, Giambanco I (2009) S100B’s double life: intracellular regulator and extracellular signal. Biochim Biophys Acta 1793(6):1008–1022. doi:10.1016/j.bbamcr.2008.11.009

    Article  CAS  PubMed  Google Scholar 

  76. Teeling JL, Perry VH (2009) Systemic infection and inflammation in acute CNS injury and chronic neurodegeneration: underlying mechanisms. Neuroscience 158(3):1062–1073. doi:10.1016/j.neuroscience.2008.07.031

    Article  CAS  PubMed  Google Scholar 

  77. Doyle KP, Cekanaviciute E, Mamer LE, Buckwalter MS (2010) TGFbeta signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke. J Neuroinflammation 7:62. doi:10.1186/1742-2094-7-62

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work 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), Financiadora de Estudos e Projetos (FINEP) – IBN Net (Instituto Brasileiro de Neurociências) 01.06.0842-00, Federal University of Rio Grande do Sul (UFRGS), and Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção (INCTEN/CNPq).

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  1. Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 – Anexo, Bairro Santa Cecília, Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

    Bruna Bellaver, Débora Guerini Souza, Diogo Onofre Souza & André Quincozes-Santos

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  1. Bruna Bellaver
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Bellaver, B., Souza, D.G., Souza, D.O. et al. Hippocampal Astrocyte Cultures from Adult and Aged Rats Reproduce Changes in Glial Functionality Observed in the Aging Brain. Mol Neurobiol 54, 2969–2985 (2017). https://doi.org/10.1007/s12035-016-9880-8

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