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Downregulation of hippocampal NR2A/2B subunits related to cognitive impairment in a pristane-induced lupus BALB/c mice


Autoři: Jonatan Luciano-Jaramillo aff001;  Flavio Sandoval-García aff001;  Mónica Vázquez-Del Mercado aff001;  Yanet Karina Gutiérrez-Mercado aff006;  Rosa Elena Navarro-Hernández aff001;  Erika Aurora Martínez-García aff001;  Oscar Pizano-Martínez aff001;  Fernanda Isadora Corona-Meraz aff001;  Jacinto Bañuelos-Pineda aff008;  Jorge Fernando Floresvillar-Mosqueda aff009;  Beatriz Teresita Martín-Márquez aff001
Působiště autorů: Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Departamento de Biología Molecular y Genómica, Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético (IIRSME), Guadalajara, Jalisco, CP, México aff001;  Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Departamento de Clínicas Médicas, Guadalajara, Jalisco, CP, México aff002;  Universidad de Guadalajara, Envejecimiento, inmuno-metabolismo y estrés oxidativo, Guadalajara, Jalisco, CP, México aff003;  Hospital Civil de Guadalajara, Dr. Juan I. Menchaca, División de Medicina Interna, Servicio de Reumatología, Guadalajara, Jalisco, CP, México aff004;  Universidad de Guadalajara, Inmunología y Reumatología, Guadalajara, Jalisco, CP, México aff005;  Unidad de Evaluación Preclínica, Biotecnología Médica y Farmacéutica, CONACYT Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Guadalajara, CP, México aff006;  Universidad de Guadalajara, Centro Universitario de Tonalá, Departamento de Ciencias Biomédicas, División de Ciencias de la Salud, Tonalá, Jalisco, CP, México aff007;  Universidad de Guadalajara, Centro Universitario de Ciencias Biológicas y Agropecuarias, Departamento de Medicina Veterinaria, Zapopan, Jalisco, CP, México aff008;  Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Departamento de Microbiología, Guadalajara, Jalisco, CP, México aff009
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0217190

Souhrn

Neuropsychiatric systemic lupus erythematosus (NPSLE) is associated with learning and memory deficit. Murine model of lupus induced by pristane in BALB/c mice is an experimental model that resembles some clinical and immunological SLE pathogenesis. Nevertheless, there is no experimental evidence that relates this model to cognitive dysfunction associated with NR2A/2B relative expression. To evaluate cognitive impairment related to memory deficits in a murine model of lupus induced by pristane in BALB/c mice related to mRNA relative expression levels of NR2A/2B hippocampal subunits in short and long-term memory task at 7 and 12 weeks after LPS exposition in a behavioral test with the use of Barnes maze. A total of 54 female BALB/c mice 8–12 weeks old were included into 3 groups: 7 and 12 weeks using pristane alone (0.5 mL of pristane) by a single intraperitoneal (i.p.) injection. A control group (single i.p. injection of 0.5 mL NaCl 0.9%) and pristane plus LPS exposure using single i.p. pristane injection and LPS of E. coli O55:B5, in a dose of 3mg/kg diluted in NaCl 0.9% 16 weeks post-pristane administration. To determine cognitive dysfunction, mice were tested in a Barnes maze. Serum anti-Sm antibodies and relative expression of hippocampal NR2A/2B subunits (GAPDH as housekeeping gene) with SYBR green quantitative reverse transcription polymerase chain reaction and 2-ΔΔCT method were determined in the groups. Downregulation of hippocampal NR2A subunit was more evident than NR2B in pristane and pristane+LPS at 7 and 12 weeks of treatment and it is related to learning and memory disturbance assayed by Barnes maze. This is the first report using the murine model of lupus induced by pristane that analyzes the NMDA subunit receptors, finding a downregulation of NR2A subunit related to learning and memory disturbance being more evident when they were exposed to LPS.

Klíčová slova:

Biology and life sciences – Biochemistry – Organisms – Eukaryota – Research and analysis methods – Animal studies – Experimental organism systems – Model organisms – Proteins – Neuroscience – Cognitive science – Cognitive psychology – Learning – Learning and memory – Psychology – Animals – Social sciences – Animal models – Medicine and health sciences – Physiology – Vertebrates – Amniotes – Mammals – Zoology – Rheumatology – Clinical medicine – Clinical immunology – Autoimmune diseases – Immunology – Immune physiology – Neurology – Cognitive neurology – Cognitive impairment – Cognitive neuroscience – Immune system proteins – Antibodies – Behavior – Mouse models – Immunologic techniques – Immunoassays – Enzyme-linked immunoassays – Rodents – Mice – Autoantibodies – Animal behavior – Lupus erythematosus – Systemic lupus erythematosus


Zdroje

1. Mahler M. Sm peptides in differentiation of autoimmune diseases. Adv Clin Chem. 2011;54:109–28. 21874759

2. Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677–86. doi: 10.1002/art.34473 22553077

3. Zardi EM, Taccone A, Marigliano B, Margiotta DP, Afeltra A. Neuropsychiatric systemic lupus erythematosus: tools for the diagnosis. Autoimmun Rev. 2014;13(8):831–9. doi: 10.1016/j.autrev.2014.04.002 24704869

4. Diamond B, Volpe BT. A model for lupus brain disease. Immunol Rev. 2012;248(1):56–67. doi: 10.1111/j.1600-065X.2012.01137.x 22725954

5. Sciascia S, Bertolaccini ML, Roccatello D, Khamashta MA, Sanna G. Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus: a systematic review. J Neurol. 2014;261(9):1706–14. doi: 10.1007/s00415-014-7406-8 24952022

6. Briani C, Lucchetta M, Ghirardello A, Toffanin E, Zampieri S, Ruggero S, et al. Neurolupus is associated with anti-ribosomal P protein antibodies: an inception cohort study. J Autoimmun. 2009;32(2):79–84. doi: 10.1016/j.jaut.2008.12.002 19171463

7. Vivaldo JF, de Amorim JC, Julio PR, de Oliveira RJ, Appenzeller S. Definition of NPSLE: Does the ACR Nomenclature Still Hold? Front Med (Lausanne). 2018;5:138.

8. Pikman R, Kivity S, Levy Y, Arango MT, Chapman J, Yonath H, et al. Neuropsychiatric SLE: from animal model to human. Lupus. 2017;26(5):470–7. doi: 10.1177/0961203317694261 28394237

9. Aranow C, Diamond B, Mackay M. Glutamate receptor biology and its clinical significance in neuropsychiatric systemic lupus erythematosus. Rheum Dis Clin North Am. 2010;36(1):187–201, x-xi. doi: 10.1016/j.rdc.2009.12.007 20202599

10. DeGiorgio LA, Konstantinov KN, Lee SC, Hardin JA, Volpe BT, Diamond B. A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med. 2001;7(11):1189–93. doi: 10.1038/nm1101-1189 11689882

11. Bosch X, Ramos-Casals M, Khamashta MA. The DWEYS peptide in systemic lupus erythematosus. Trends Mol Med. 2012;18(4):215–23. doi: 10.1016/j.molmed.2012.01.008 22365619

12. Satoh M, Reeves WH. Induction of lupus-associated autoantibodies in BALB/c mice by intraperitoneal injection of pristane. J Exp Med. 1994;180(6):2341–6. doi: 10.1084/jem.180.6.2341 7964507

13. Reeves WH, Lee PY, Weinstein JS, Satoh M, Lu L. Induction of autoimmunity by pristane and other naturally occurring hydrocarbons. Trends Immunol. 2009;30(9):455–64. doi: 10.1016/j.it.2009.06.003 19699150

14. Freitas EC, de Oliveira MS, Monticielo OA. Pristane-induced lupus: considerations on this experimental model. Clin Rheumatol. 2017;36(11):2403–14. doi: 10.1007/s10067-017-3811-6 28879482

15. Vo A, Volpe BT, Tang CC, Schiffer WK, Kowal C, Huerta PT, et al. Regional brain metabolism in a murine systemic lupus erythematosus model. J Cereb Blood Flow Metab. 2014;34(8):1315–20. doi: 10.1038/jcbfm.2014.85 24824914

16. Barnes CA. Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol. 1979;93(1):74–104. doi: 10.1037/h0077579 221551

17. Gawel K, Gibula E, Marszalek-Grabska M, Filarowska J, Kotlinska JH. Assessment of spatial learning and memory in the Barnes maze task in rodents-methodological consideration. Naunyn Schmiedebergs Arch Pharmacol. 2019;392(1):1–18. doi: 10.1007/s00210-018-1589-y 30470917

18. Hamada S, Ogawa I, Yamasaki M, Kiyama Y, Kassai H, Watabe AM, et al. The glutamate receptor GluN2 subunit regulates synaptic trafficking of AMPA receptors in the neonatal mouse brain. Eur J Neurosci. 2014;40(8):3136–46. doi: 10.1111/ejn.12682 25131300

19. Duarte-Garcia A, Romero-Diaz J, Juarez S, Cicero-Casarrubias A, Fragoso-Loyo H, Nunez-Alvarez C, et al. Disease activity, autoantibodies, and inflammatory molecules in serum and cerebrospinal fluid of patients with Systemic Lupus Erythematosus and Cognitive Dysfunction. PLoS One. 2018;13(5):e0196487. doi: 10.1371/journal.pone.0196487 29723220

20. Faust TW, Chang EH, Kowal C, Berlin R, Gazaryan IG, Bertini E, et al. Neurotoxic lupus autoantibodies alter brain function through two distinct mechanisms. Proc Natl Acad Sci U S A. 2010;107(43):18569–74. doi: 10.1073/pnas.1006980107 20921396

21. Hirohata S, Sakuma Y, Yanagida T, Yoshio T. Association of cerebrospinal fluid anti-Sm antibodies with acute confusional state in systemic lupus erythematosus. Arthritis Res Ther. 2014;16(5):450. doi: 10.1186/s13075-014-0450-z 25273532

22. Hirohata S, Sakuma Y, Matsueda Y, Arinuma Y, Yanagida T. Role of serum autoantibodies in blood brain barrier damages in neuropsychiatric systemic lupus erythematosus. Clin Exp Rheumatol. 2018;36(6):1003–7 29846157

23. Bluestein HG, Williams GW, Steinberg AD. Cerebrospinal fluid antibodies to neuronal cells: association with neuropsychiatric manifestations of systemic lupus erythematosus. Am J Med. 1981;70(2):240–6. doi: 10.1016/0002-9343(81)90756-7 7468611

24. How A, Dent PB, Liao SK, Denburg JA. Antineuronal antibodies in neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 1985;28(7):789–95. doi: 10.1002/art.1780280710 4015726

25. Massardo L, Bravo-Zehnder M, Calderon J, Flores P, Padilla O, Aguirre JM, et al. Anti-N-methyl-D-aspartate receptor and anti-ribosomal-P autoantibodies contribute to cognitive dysfunction in systemic lupus erythematosus. Lupus. 2015;24(6):558–68. doi: 10.1177/0961203314555538 25318968

26. Yang Y, Yuan C, Shen SQ, Wang XE, Mei QH, Jiang WQ, et al. Autoantibodies to NR2A Peptide of the Glutamate/NMDA Receptor in Patients with Seizure Disorders in Neuropsychiatric Systemic Lupus Erythematosus. Mediators Inflamm. 2017;2017:5047898. doi: 10.1155/2017/5047898 28154472

27. Ogawa E, Nagai T, Sakuma Y, Arinuma Y, Hirohata S. Association of antibodies to the NR1 subunit of N-methyl-D-aspartate receptors with neuropsychiatric systemic lupus erythematosus. Mod Rheumatol. 2016;26(3):377–83. doi: 10.3109/14397595.2015.1083163 26429674

28. Magro-Checa C, Kumar S, Ramiro S, Beaart-van de Voorde LJ, Eikenboom J, Ronen I, et al. Are serum autoantibodies associated with brain changes in systemic lupus erythematosus? MRI data from the Leiden NP-SLE cohort. Lupus. 2019;28(1):94–103. doi: 10.1177/0961203318816819 30526327

29. Chi JM, Mackay M, Hoang A, Cheng K, Aranow C, Ivanidze J, et al. Alterations in Blood-Brain Barrier Permeability in Patients with Systemic Lupus Erythematosus. AJNR Am J Neuroradiol. 2019;40(3):470–7. doi: 10.3174/ajnr.A5990 30792254

30. O'Leary TP, Savoie V, Brown RE. Learning, memory and search strategies of inbred mouse strains with different visual abilities in the Barnes maze. Behav Brain Res. 2011;216(2):531–42. doi: 10.1016/j.bbr.2010.08.030 20801160

31. Harrison FE, Hosseini AH, McDonald MP. Endogenous anxiety and stress responses in water maze and Barnes maze spatial memory tasks. Behav Brain Res. 2009;198(1):247–51. doi: 10.1016/j.bbr.2008.10.015 18996418

32. Maher A, El-Sayed NS, Breitinger HG, Gad MZ. Overexpression of NMDAR2B in an inflammatory model of Alzheimer's disease: modulation by NOS inhibitors. Brain Res Bull. 2014;109:109–16. doi: 10.1016/j.brainresbull.2014.10.007 25454121

33. Brigman JL, Feyder M, Saksida LM, Bussey TJ, Mishina M, Holmes A. Impaired discrimination learning in mice lacking the NMDA receptor NR2A subunit. Learn Mem. 2008;15(2):50–4. doi: 10.1101/lm.777308 18230672

34. Quinlan EM, Lebel D, Brosh I, Barkai E. A molecular mechanism for stabilization of learning-induced synaptic modifications. Neuron. 2004;41(2):185–92. doi: 10.1016/s0896-6273(03)00874-2 14741100

35. Boyce-Rustay JM, Holmes A. Genetic inactivation of the NMDA receptor NR2A subunit has anxiolytic- and antidepressant-like effects in mice. Neuropsychopharmacology. 2006;31(11):2405–14. doi: 10.1038/sj.npp.1301039 16482087

36. Mader S, Brimberg L, Diamond B. The Role of Brain-Reactive Autoantibodies in Brain Pathology and Cognitive Impairment. Front Immunol. 2017;8:1101. doi: 10.3389/fimmu.2017.01101 28955334


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