Systemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas

The receptor for advanced glycation endproducts (RAGE) is a transmembrane, immunoglobulin-like receptor that interacts with a broad repertoire of extracellular ligands. RAGE belongs to a family of cell adhesion molecules and is considered a key receptor in the inflammation axis and a potential contr...

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Autores:
Gasparotto, Juciano
Ribeiro Tiefensee, Camila
Da Rosa Siva, Helen Tais
Bortolin, Rafael Calixto
Rabelo, Thallita Kelly
Peixoto, Daniel Oppermann
Moreira Fonseca, José Cláudio
Gelain, D. P.
Tipo de recurso:
Article of journal
Fecha de publicación:
2018
Institución:
Corporación Universidad de la Costa
Repositorio:
REDICUC - Repositorio CUC
Idioma:
eng
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oai:repositorio.cuc.edu.co:11323/1858
Acceso en línea:
https://hdl.handle.net/11323/1858
https://doi.org/10.1007/s12035-018-1291-6.
https://repositorio.cuc.edu.co/
Palabra clave:
Dopaminergic cells
Endothelial cells
Neurodegeneration
Neuroinflammation
RAGE
Substantia nigra
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openAccess
License
Atribución – No comercial – Compartir igual
id RCUC2_d437107aa17f129f033e62aca6244cdc
oai_identifier_str oai:repositorio.cuc.edu.co:11323/1858
network_acronym_str RCUC2
network_name_str REDICUC - Repositorio CUC
repository_id_str
dc.title.eng.fl_str_mv Systemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas
title Systemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas
spellingShingle Systemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas
Dopaminergic cells
Endothelial cells
Neurodegeneration
Neuroinflammation
RAGE
Substantia nigra
title_short Systemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas
title_full Systemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas
title_fullStr Systemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas
title_full_unstemmed Systemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas
title_sort Systemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas
dc.creator.fl_str_mv Gasparotto, Juciano
Ribeiro Tiefensee, Camila
Da Rosa Siva, Helen Tais
Bortolin, Rafael Calixto
Rabelo, Thallita Kelly
Peixoto, Daniel Oppermann
Moreira Fonseca, José Cláudio
Gelain, D. P.
dc.contributor.author.spa.fl_str_mv Gasparotto, Juciano
Ribeiro Tiefensee, Camila
Da Rosa Siva, Helen Tais
Bortolin, Rafael Calixto
Rabelo, Thallita Kelly
Peixoto, Daniel Oppermann
Moreira Fonseca, José Cláudio
Gelain, D. P.
dc.subject.eng.fl_str_mv Dopaminergic cells
Endothelial cells
Neurodegeneration
Neuroinflammation
RAGE
Substantia nigra
topic Dopaminergic cells
Endothelial cells
Neurodegeneration
Neuroinflammation
RAGE
Substantia nigra
description The receptor for advanced glycation endproducts (RAGE) is a transmembrane, immunoglobulin-like receptor that interacts with a broad repertoire of extracellular ligands. RAGE belongs to a family of cell adhesion molecules and is considered a key receptor in the inflammation axis and a potential contributor to the neurodegeneration. The present study aimed to investigate the content and cell localization of RAGE in the brain of Wistar rats subjected to systemic inflammation induced by a single dose of lipopolysaccharide (LPS, 5 mg/kg, i.p.). Fifteen days after LPS administration, the content of RAGE was analyzed in the prefrontal cortex (PFC), hippocampus (HIPP), cerebellum (CB), and substantia nigra (SN) were investigated. RAGE levels increased in all structures, except HIPP; however, immunohistochemistry analysis demonstrated that the cell site of RAGE expression changed from blood vessel-like structures to neuronal cells in all brain areas. Besides, the highest level of RAGE expression was found in SN. Immunofluorescence analysis in SN confirmed that RAGE expression was mainly co-localized in endothelial cells (RAGE/PECAM-1 co-staining) in untreated animals, while LPS-treated animals had RAGE expression predominantly in dopaminergic neurons (RAGE/TH co-staining). Decreased TH levels, as well as increased pro-inflammatory markers (TNF-α, IL-1β, Iba-1, GFAP, and phosphorylated ERK1/2) in SN, occurred concomitantly to RAGE stimulation in the same site. These results suggest a role for RAGE in the establishment of a neuroinflammation-neurodegeneration axis that develops as a long-term response to systemic inflammation by LPS.
publishDate 2018
dc.date.accessioned.none.fl_str_mv 2018-11-26T15:41:31Z
dc.date.available.none.fl_str_mv 2018-11-26T15:41:31Z
dc.date.issued.none.fl_str_mv 2019
dc.type.spa.fl_str_mv Artículo de revista
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.type.content.spa.fl_str_mv Text
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dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
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dc.identifier.issn.spa.fl_str_mv 08937648
dc.identifier.uri.spa.fl_str_mv https://hdl.handle.net/11323/1858
dc.identifier.doi.spa.fl_str_mv https://doi.org/10.1007/s12035-018-1291-6.
dc.identifier.instname.spa.fl_str_mv Corporación Universidad de la Costa
dc.identifier.reponame.spa.fl_str_mv REDICUC - Repositorio CUC
dc.identifier.repourl.spa.fl_str_mv https://repositorio.cuc.edu.co/
identifier_str_mv 08937648
Corporación Universidad de la Costa
REDICUC - Repositorio CUC
url https://hdl.handle.net/11323/1858
https://doi.org/10.1007/s12035-018-1291-6.
https://repositorio.cuc.edu.co/
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.references.spa.fl_str_mv 1. Sessa L, Gatti E, Zeni F, Antonelli A, Catucci A, Koch M, Pompilio G, Fritz G et al (2014) The receptor for advanced glycation endproducts (RAGE) is only present in mammals, and belongs to a family of cell adhesion molecules (CAMs). PLoS One 9(1): e86903. https://doi.org/10.1371/journal.pone.0086903 2. Chuah YK, Basir R, Talib H, Tie TH, Nordin N (2013) Receptor for advanced glycation end products and its involvement in inflammatory diseases. Int J Inflamm 2013:403460. https://doi.org/10.1155/ 2013/403460 3. Gasparotto J, Ribeiro CT, Bortolin RC, Somensi N, Rabelo TK, Kunzler A, Souza NC, Pasquali MAB et al (2017) Targeted inhibition of RAGE in substantia nigra of rats blocks 6-OHDA-induced dopaminergic denervation. Sci Rep 7(1):8795. https://doi.org/10. 1038/s41598-017-09257-3 4. Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B, Love R, Perry S et al (2012) A multimodal RAGE-specific inhibitor reduces amyloid beta-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest 122(4):1377–1392. https://doi. org/10.1172/jci58642 5. Buckley ST, Ehrhardt C (2010) The receptor for advanced glycation end products (RAGE) and the lung. J Biomed Biotechnol 2010: 917108–917111. https://doi.org/10.1155/2010/917108 6. Fritz G (2011) RAGE: a single receptor fits multiple ligands. Trends Biochem Sci 36(12):625–632. https://doi.org/10.1016/j.tibs.2011. 08.008 7. Gasiorowski K, Brokos B, Echeverria V, Barreto GE, Leszek J (2018) RAGE-TLR crosstalk sustains chronic inflammation in neurodegeneration. Mol Neurobiol 55(2):1463–1476. https://doi.org/ 10.1007/s12035-017-0419-4 8. Yamamoto Y, Harashima A, Saito H, Tsuneyama K, Munesue S, Motoyoshi S, Han D, Watanabe T et al (2011) Septic shock is associated with receptor for advanced glycation end products ligation of LPS. J Immunol 186(5):3248–3257. https://doi.org/10.4049/ jimmunol.1002253 9. Somensi N, Brum PO, de Miranda RV, Gasparotto J, Zanotto-Filho A, Rostirolla DC, da Silva MM, Moreira JCF et al (2017) Extracellular HSP70 activates ERK1/2, NF-kB and proinflammatory gene transcription through binding with RAGE in A549 human lung cancer cells. Cell Physiol and Biochem 42(6): 2507–2522. https://doi.org/10.1159/000480213 10. Grunwald MS, Ligabue-Braun R, Souza CS, Heimfarth L, Verli H, Gelain DP, Moreira JC (2017) Putative model for heat shock protein 70 complexation with receptor of advanced glycation end products Mol Neurobiol through fluorescence proximity assays and normal mode analyses. Cell Stress Chaperones 22(1):99–111. https://doi.org/10.1007/ s12192-016-0746-9 11. Zhang H, Wang Y, Yan S, Du F, Wu L, Yan SS (2014) Genetic deficiency of neuronal RAGE protects against AGE-induced synaptic injury. Cell Death Dis 5:e1288. https://doi.org/10.1038/cddis. 2014.248 12. McKenzie JA, Spielman LJ, Pointer CB, Lowry JR, Bajwa E, Lee CW, Klegeris A (2017) Neuroinflammation as a common mechanism associated with the modifiable risk factors for Alzheimer’s and Parkinson’s diseases. Curr Aging Sci 10(3):158–176. https://doi. org/10.2174/1874609810666170315113244 13. Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55(5):453–462. https:// doi.org/10.1002/glia.20467 14. Gasparotto J, Girardi CS, Somensi N, Ribeiro CT, Moreira JCF, Michels M, Sonai B, Rocha M et al (2018) Receptor for advanced glycation end products mediates sepsis-triggered amyloid-beta accumulation, Tau phosphorylation, and cognitive impairment. J Biol Chem 293(1):226–244. https://doi.org/10.1074/jbc.M117.786756 15. Gasparotto J, Ribeiro CT, Bortolin RC, Somensi N, Fernandes HS, Teixeira AA, Guasselli MOR, Agani C et al (2017) Anti-RAGE antibody selectively blocks acute systemic inflammatory responses to LPS in serum, liver, CSF and striatum. Brain Behav Immun 62: 124–136. https://doi.org/10.1016/j.bbi.2017.01.008 16. National Research Council (2011). Guide laboratory animals for the care and use of eighth edition. Accessed: 05/31/2018. Available: https://grants.nih.gov/grants/olaw/guide-for-the-care-and-use-oflaboratory-animals.pdf 17. Gasparotto J, Senger MR, Kunzler A, Degrossoli A, de Simone SG, Bortolin RC, Somensi N, Girardi CS et al (2015) Increased tau phosphorylation and receptor for advanced glycation endproducts (RAGE) in the brain of mice infected with Leishmania amazonensis. Brain Behav Immun 43:37–45. https://doi.org/10. 1016/j.bbi.2014.06.204 18. Gage GJ, Kipke DR, Shain W (2012) Whole animal perfusion fixation for rodents. J Vis Exp 65. https://doi.org/10.3791/3564 19. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10. 1016/0003-2697(76)90527-3 20. Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Elsevier 21. Ray R, Juranek JK, Rai V (2016) RAGE axis in neuroinflammation, neurodegeneration and its emerging role in the pathogenesis of amyotrophic lateral sclerosis. Neurosci Biobehav Rev 62:48–55. https://doi.org/10.1016/j.neubiorev.2015.12.006 22. Candela P, Gosselet F, Saint-Pol J, Sevin E, Boucau MC, Boulanger E, Cecchelli R, Fenart L (2010) Apical-to-basolateral transport of amyloid-beta peptides through blood-brain barrier cells is mediated by the receptor for advanced glycation end-products and is restricted by P-glycoprotein. J Alzheimers Dis 22(3):849–859. https://doi.org/10.3233/JAD-2010-100462 23. Ding Q, Keller JN (2005) Evaluation of rage isoforms, ligands, and signaling in the brain. Biochim Biophys Acta 1746(1):18–27. https://doi.org/10.1016/j.bbamcr.2005.08.006 24. Song J, Lee WT, Park KA, Lee JE (2014) Receptor for advanced glycation end products (RAGE) and its ligands: focus on spinal cord injury. Int J Mol Sci 15(8):13172–13191. https://doi.org/10. 3390/ijms150813172 25. Wang L, Wu J, Guo X, Huang X, Huang Q (2017) RAGE plays a role in LPS-induced NF-κB activation and endothelial hyperpermeability. Sensors (Basel) 17(4). https://doi.org/10.3390/ s17040722 26. Chavakis T, Bierhaus A, Al-Fakhri N, Schneider D, Witte S, Linn T, Nagashima M, Morser J et al (2003) The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med 198(10): 1507–1515. https://doi.org/10.1084/jem.20030800 27. Aronson D, Rayfield EJ (2002) How hyperglycemia promotes atherosclerosis: molecular mechanisms. Cardiovasc Diabetol 1:1. https://doi.org/10.1186/1475-2840-1-1 28. Avignone E, Lepleux M, Angibaud J, Nägerl UV (2015) Altered morphological dynamics of activated microglia after induction of status epilepticus. J Neuroinflammation 12:202. https://doi.org/10. 1186/s12974-015-0421-6 29. Luo XG, Chen SD (2012) The changing phenotype of microglia from homeostasis to disease. Transl Neurodegener 1:9. https://doi. org/10.1186/2047-9158-1-9 30. Gasparotto J, Girardi CS, Somensi N, Ribeiro CT, Moreira JCF, Michels M, Sonai B, Rocha M et al (2018) Receptor for advanced glycation end products mediates sepsis-triggered amyloid-β accumulation, Tau phosphorylation, and cognitive impairment. J Biol Chem 293(1):226–244. https://doi.org/10.1074/jbc.M117.786756 31. Lopresti ST, Brown BN (2015) Chapter 4 - Host response to naturally derived biomaterials. In: Badylak SF (ed) Host response to biomaterials. Academic Press, Oxford, pp. 53–79 32. Ishihara K, Tsutsumi K, Kawane S, Nakajima M, Kasaoka T (2003) The receptor for advanced glycation end-products (RAGE) directly binds to ERK by a D-domain-like docking site. FEBS Lett 550(1– 3):107–113. https://doi.org/10.1016/S0014-5793(03)00846-9 33. Tobon-Velasco JC, Cuevas E, Torres-Ramos MA (2014) Receptor for AGEs (RAGE) as mediator of NF-kB pathway activation in neuroinflammation and oxidative stress. CNS Neurol Disord Drug Targets 13(9):1615–1626. https://doi. org/10.2174/1871527313666140806144831 34. Hoban DB, Connaughton E, Connaughton C, Hogan G, Thornton C, Mulcahy P, Moloney TC, Dowd E (2013) Further characterization of the LPS model of Parkinson’s disease: a comparison of intranigral and intra-striatal lipopolysaccharide administration on motor function, microgliosis and nigrostriatal neurodegeneration in the rat. Brain Behav Immun 27(1):91–100. https://doi.org/10.1016/j. bbi.2012.10.001
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spelling Gasparotto, JucianoRibeiro Tiefensee, CamilaDa Rosa Siva, Helen TaisBortolin, Rafael CalixtoRabelo, Thallita KellyPeixoto, Daniel OppermannMoreira Fonseca, José CláudioGelain, D. P.2018-11-26T15:41:31Z2018-11-26T15:41:31Z201908937648https://hdl.handle.net/11323/1858https://doi.org/10.1007/s12035-018-1291-6.Corporación Universidad de la CostaREDICUC - Repositorio CUChttps://repositorio.cuc.edu.co/The receptor for advanced glycation endproducts (RAGE) is a transmembrane, immunoglobulin-like receptor that interacts with a broad repertoire of extracellular ligands. RAGE belongs to a family of cell adhesion molecules and is considered a key receptor in the inflammation axis and a potential contributor to the neurodegeneration. The present study aimed to investigate the content and cell localization of RAGE in the brain of Wistar rats subjected to systemic inflammation induced by a single dose of lipopolysaccharide (LPS, 5 mg/kg, i.p.). Fifteen days after LPS administration, the content of RAGE was analyzed in the prefrontal cortex (PFC), hippocampus (HIPP), cerebellum (CB), and substantia nigra (SN) were investigated. RAGE levels increased in all structures, except HIPP; however, immunohistochemistry analysis demonstrated that the cell site of RAGE expression changed from blood vessel-like structures to neuronal cells in all brain areas. Besides, the highest level of RAGE expression was found in SN. Immunofluorescence analysis in SN confirmed that RAGE expression was mainly co-localized in endothelial cells (RAGE/PECAM-1 co-staining) in untreated animals, while LPS-treated animals had RAGE expression predominantly in dopaminergic neurons (RAGE/TH co-staining). Decreased TH levels, as well as increased pro-inflammatory markers (TNF-α, IL-1β, Iba-1, GFAP, and phosphorylated ERK1/2) in SN, occurred concomitantly to RAGE stimulation in the same site. These results suggest a role for RAGE in the establishment of a neuroinflammation-neurodegeneration axis that develops as a long-term response to systemic inflammation by LPS.Gasparotto, Juciano-a7ba2163-3c88-45e4-b4f0-627833f8b03f-0Ribeiro Tiefensee, Camila-556dc801-93ad-48f0-846a-627ead70b4d6-0Da Rosa Siva, Helen Tais-fba50b96-8879-4ba1-ab4c-cb26d9ae97b4-0Bortolin, Rafael Calixto-0000-0003-4780-8499-600Rabelo, Thallita Kelly-3cca46bc-d2d5-4941-8fff-bd3b0074486b-0Peixoto, Daniel Oppermann-3e901c77-f76d-42cc-bb51-b45a10e5d838-0Moreira Fonseca, José Cláudio-4373df94-e345-42b4-861c-55953fd27b36-0Gelain, D. P.-6c9b4902-cbb1-4e61-bff7-ad547ff8429c-0engMolecular NeurobiologyAtribución – No comercial – Compartir igualinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Dopaminergic cellsEndothelial cellsNeurodegenerationNeuroinflammationRAGESubstantia nigraSystemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain AreasArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/acceptedVersion1. Sessa L, Gatti E, Zeni F, Antonelli A, Catucci A, Koch M, Pompilio G, Fritz G et al (2014) The receptor for advanced glycation endproducts (RAGE) is only present in mammals, and belongs to a family of cell adhesion molecules (CAMs). PLoS One 9(1): e86903. https://doi.org/10.1371/journal.pone.0086903 2. Chuah YK, Basir R, Talib H, Tie TH, Nordin N (2013) Receptor for advanced glycation end products and its involvement in inflammatory diseases. Int J Inflamm 2013:403460. https://doi.org/10.1155/ 2013/403460 3. Gasparotto J, Ribeiro CT, Bortolin RC, Somensi N, Rabelo TK, Kunzler A, Souza NC, Pasquali MAB et al (2017) Targeted inhibition of RAGE in substantia nigra of rats blocks 6-OHDA-induced dopaminergic denervation. Sci Rep 7(1):8795. https://doi.org/10. 1038/s41598-017-09257-3 4. Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B, Love R, Perry S et al (2012) A multimodal RAGE-specific inhibitor reduces amyloid beta-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest 122(4):1377–1392. https://doi. org/10.1172/jci58642 5. Buckley ST, Ehrhardt C (2010) The receptor for advanced glycation end products (RAGE) and the lung. J Biomed Biotechnol 2010: 917108–917111. https://doi.org/10.1155/2010/917108 6. Fritz G (2011) RAGE: a single receptor fits multiple ligands. Trends Biochem Sci 36(12):625–632. https://doi.org/10.1016/j.tibs.2011. 08.008 7. Gasiorowski K, Brokos B, Echeverria V, Barreto GE, Leszek J (2018) RAGE-TLR crosstalk sustains chronic inflammation in neurodegeneration. Mol Neurobiol 55(2):1463–1476. https://doi.org/ 10.1007/s12035-017-0419-4 8. Yamamoto Y, Harashima A, Saito H, Tsuneyama K, Munesue S, Motoyoshi S, Han D, Watanabe T et al (2011) Septic shock is associated with receptor for advanced glycation end products ligation of LPS. J Immunol 186(5):3248–3257. https://doi.org/10.4049/ jimmunol.1002253 9. Somensi N, Brum PO, de Miranda RV, Gasparotto J, Zanotto-Filho A, Rostirolla DC, da Silva MM, Moreira JCF et al (2017) Extracellular HSP70 activates ERK1/2, NF-kB and proinflammatory gene transcription through binding with RAGE in A549 human lung cancer cells. Cell Physiol and Biochem 42(6): 2507–2522. https://doi.org/10.1159/000480213 10. Grunwald MS, Ligabue-Braun R, Souza CS, Heimfarth L, Verli H, Gelain DP, Moreira JC (2017) Putative model for heat shock protein 70 complexation with receptor of advanced glycation end products Mol Neurobiol through fluorescence proximity assays and normal mode analyses. Cell Stress Chaperones 22(1):99–111. https://doi.org/10.1007/ s12192-016-0746-9 11. Zhang H, Wang Y, Yan S, Du F, Wu L, Yan SS (2014) Genetic deficiency of neuronal RAGE protects against AGE-induced synaptic injury. Cell Death Dis 5:e1288. https://doi.org/10.1038/cddis. 2014.248 12. McKenzie JA, Spielman LJ, Pointer CB, Lowry JR, Bajwa E, Lee CW, Klegeris A (2017) Neuroinflammation as a common mechanism associated with the modifiable risk factors for Alzheimer’s and Parkinson’s diseases. Curr Aging Sci 10(3):158–176. https://doi. org/10.2174/1874609810666170315113244 13. Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55(5):453–462. https:// doi.org/10.1002/glia.20467 14. Gasparotto J, Girardi CS, Somensi N, Ribeiro CT, Moreira JCF, Michels M, Sonai B, Rocha M et al (2018) Receptor for advanced glycation end products mediates sepsis-triggered amyloid-beta accumulation, Tau phosphorylation, and cognitive impairment. J Biol Chem 293(1):226–244. https://doi.org/10.1074/jbc.M117.786756 15. Gasparotto J, Ribeiro CT, Bortolin RC, Somensi N, Fernandes HS, Teixeira AA, Guasselli MOR, Agani C et al (2017) Anti-RAGE antibody selectively blocks acute systemic inflammatory responses to LPS in serum, liver, CSF and striatum. Brain Behav Immun 62: 124–136. https://doi.org/10.1016/j.bbi.2017.01.008 16. National Research Council (2011). Guide laboratory animals for the care and use of eighth edition. Accessed: 05/31/2018. Available: https://grants.nih.gov/grants/olaw/guide-for-the-care-and-use-oflaboratory-animals.pdf 17. Gasparotto J, Senger MR, Kunzler A, Degrossoli A, de Simone SG, Bortolin RC, Somensi N, Girardi CS et al (2015) Increased tau phosphorylation and receptor for advanced glycation endproducts (RAGE) in the brain of mice infected with Leishmania amazonensis. Brain Behav Immun 43:37–45. https://doi.org/10. 1016/j.bbi.2014.06.204 18. Gage GJ, Kipke DR, Shain W (2012) Whole animal perfusion fixation for rodents. J Vis Exp 65. https://doi.org/10.3791/3564 19. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10. 1016/0003-2697(76)90527-3 20. Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Elsevier 21. Ray R, Juranek JK, Rai V (2016) RAGE axis in neuroinflammation, neurodegeneration and its emerging role in the pathogenesis of amyotrophic lateral sclerosis. Neurosci Biobehav Rev 62:48–55. https://doi.org/10.1016/j.neubiorev.2015.12.006 22. Candela P, Gosselet F, Saint-Pol J, Sevin E, Boucau MC, Boulanger E, Cecchelli R, Fenart L (2010) Apical-to-basolateral transport of amyloid-beta peptides through blood-brain barrier cells is mediated by the receptor for advanced glycation end-products and is restricted by P-glycoprotein. J Alzheimers Dis 22(3):849–859. https://doi.org/10.3233/JAD-2010-100462 23. Ding Q, Keller JN (2005) Evaluation of rage isoforms, ligands, and signaling in the brain. Biochim Biophys Acta 1746(1):18–27. https://doi.org/10.1016/j.bbamcr.2005.08.006 24. Song J, Lee WT, Park KA, Lee JE (2014) Receptor for advanced glycation end products (RAGE) and its ligands: focus on spinal cord injury. Int J Mol Sci 15(8):13172–13191. https://doi.org/10. 3390/ijms150813172 25. 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Brain Behav Immun 27(1):91–100. https://doi.org/10.1016/j. bbi.2012.10.001PublicationORIGINALSystemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas.pdfSystemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas.pdfapplication/pdf278983https://repositorio.cuc.edu.co/bitstreams/8d64a39f-0c5d-47e0-a527-de2cd0038cc5/downloade517bbae6cfb63c2e704ccd066d432bdMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repositorio.cuc.edu.co/bitstreams/f1fb7a28-7405-4ee1-8cfb-ee215a2c7f18/download8a4605be74aa9ea9d79846c1fba20a33MD52THUMBNAILSystemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas.pdf.jpgSystemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas.pdf.jpgimage/jpeg56499https://repositorio.cuc.edu.co/bitstreams/18c02643-bbec-4312-a39f-d059e53576cf/download82c3ac27e0dee1a4c05080b85f27d0f1MD54TEXTSystemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas.pdf.txtSystemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas.pdf.txttext/plain2130https://repositorio.cuc.edu.co/bitstreams/d9e79235-7289-4219-8bc7-33ff043f782a/downloadd28ebc5af293e92406718b1e7aba8c87MD5511323/1858oai:repositorio.cuc.edu.co:11323/18582024-09-17 14:05:44.61open.accesshttps://repositorio.cuc.edu.coRepositorio de la Universidad de la Costa CUCrepdigital@cuc.edu.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