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

• Published in: PloS one 2019-09, Vol.14 (9), p.e0217190-e0217190
• Main Authors: Luciano-Jaramillo, Jonatan, Sandoval-García, Flavio, Vázquez-Del Mercado, Mónica, Gutiérrez-Mercado, Yanet Karina, Navarro-Hernández, Rosa Elena, Martínez-García, Erika Aurora, Pizano-Martínez, Oscar, Corona-Meraz, Fernanda Isadora, Bañuelos-Pineda, Jacinto, Floresvillar-Mosqueda, Jorge Fernando, Martín-Márquez, Beatriz Teresita
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animal models; Animals; Antibodies; Arthritis; Biology and Life Sciences; Blood-brain barrier; Chronic conditions; Cognitive ability; Cognitive disorders; Cognitive Dysfunction - chemically induced; Cognitive Dysfunction - genetics; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - physiopathology; Disease Models, Animal; Disturbance; Down-Regulation; E coli; Escherichia coli; Exposure; Female; Gene Expression; Genes; Genetic aspects; Glutamic acid receptors (ionotropic); Glyceraldehyde-3-phosphate dehydrogenase; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Immunoglobulins; Immunology; Impairment; Injection; Laboratory rats; Learning; Lipopolysaccharides; Lipopolysaccharides - administration & dosage; Long term memory; Lupus; Lupus erythematosus; Lupus Erythematosus, Systemic - chemically induced; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - metabolism; Lupus Erythematosus, Systemic - physiopathology; Maze Learning; Medicine and Health Sciences; Memory; Memory Disorders - chemically induced; Memory Disorders - genetics; Memory Disorders - metabolism; Memory Disorders - physiopathology; Memory tasks; Memory, Long-Term - drug effects; Memory, Short-Term - drug effects; Mental task performance; Messenger RNA; Mice; Mice, Inbred BALB C; N-Methyl-D-aspartic acid receptors; Nervous system; Neurological complications; Pathogenesis; Polymerase chain reaction; Pristane; Receptors; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - metabolism; Research and Analysis Methods; Reverse transcription; RNA; Social Sciences; Sodium chloride; Systemic lupus erythematosus; Terpenes - administration & dosage; Transcription (Genetics)
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0217190

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.