Abstract
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.
Highlights
Cognitive impairment is associated to NR2A/2B downregulation in a pristane model of lupus 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
Systemic lupus erythematosus (SLE) is an idiopathic autoimmune disorder characterized by the induction of autoantibodies against intracellular components such as nucleosomes, double-stranded DNA and histones, and small nuclear ribonucleoproteins the more important known as Smith antigen, that is consider for the American College of Rheumatology (ACR) as a classification criteria for SLE diagnosis [1, 2]
Once the mice completed the habituation and acquisition probes in Barnes maze, we evaluated the Short Term Memory (STM) in all the groups tested at 7 weeks during D1-D4 in the exploration time to reach the target hole and enter the escape hole and we found the following statistical differences
Summary
Systemic lupus erythematosus (SLE) is an idiopathic autoimmune disorder characterized by the induction of autoantibodies against intracellular components such as nucleosomes, double-stranded DNA and histones, and small nuclear ribonucleoproteins (snRNPs) the more important (pathognomonic) known as Smith antigen (anti-Sm), that is consider for the American College of Rheumatology (ACR) as a classification criteria for SLE diagnosis [1, 2]. This condition presents a wide variety of clinical manifestations with multiple-organ affectations, especially skin and kidneys, the heart and central and/or pheripheral nervous system are implicated[3, 4]. Anti-dsDNA might cross-react with a consensus pentapeptide (DWEYS) present in NR2A and NR2B subunits of NMDA receptors, mediating neuronal loss with the consequence of a deficit in learning and memory process[4, 9,10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
