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bioRxiv · 10.1101/631879

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

Luciano-Jaramillo, J.·Sandoval-Garcia, F.·Vazquez-Del Mercado, M.·Gutierrez-Mercado, Y. K.·Navarro-Hernandez, R. E.·Martinez-Garcia, E. A.·Pizano-Martinez, O.·Corona-Meraz, F. I.·Banuelos-Pineda, J.·Floresvillar-Mosqueda, J. F.·Martin Marquez, B. T.
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Abstract

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a severe complication associated with the neurotoxic effects of circulating autoantibodies in the central nervous system (CNS) manifested frequently as a learning and memory deficit. Pristane-induced lupus in BALB/c female mice is an experimental model that resembles some clinical and immunological SLE pathogenesis associated with environmental factors. Nevertheless, there is no experimental evidence that relate pristane-induced lupus with cognitive dysfunction associated with autoantibodies production.\n\nObjectiveTo evaluate cognitive impairment related to memory deficits in a pristane-induced lupus BALB/c female mice related to mRNA expression levels of NR2A/2B hippocampal subunits in short and long-term memory task at 7 and 12 weeks after LPS exposition (7wLPS and 12wLPS) in a behavioral test with the employment of Barnes maze.\n\nMethodsFifty-four female BALB/c mice of 8-12 weeks old were included in 2 experimental groups: 7 and 12 weeks after lypopolissacharide (LPS) exposure and classified in subgroups (control, pristane and pristane+LPS). To determine cognitive dysfunction, mice were tested in a Barnes maze. Serum anti-Sm antibodies and relative expression of hippocampal NR2A/NR2B subunits were quantified.\n\nResultsPristane and pristane+LPS mice showed a prolonged escape latency at 7wLPS than at 12wLPS in short-term memory. Downregulation of hippocampal NR2A subunit was more evident than NR2B in pristane and pristane+LPS at 7wLPS and 12wLPS. The anti-Sm autoantibodies levels correlate with the relative expression of NR2A.\n\nConclusionDownregulation of hippocampal NR2A/2B subunits in the pristane-model of lupus in BALB/c mice may be related to anti-Sm autoantibodies production with the consequence of cognitive impairment in early stages of autoimmune disease.

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Luciano-Jaramillo, J., Sandoval-Garcia, F., Vazquez-Del Mercado, M., Gutierrez-Mercado, Y. K., Navarro-Hernandez, R. E., Martinez-Garcia, E. A., Pizano-Martinez, O., Corona-Meraz, F. I., Banuelos-Pineda, J., Floresvillar-Mosqueda, J. F., Martin Marquez, B. T.. 2019-05-08. Downregulation of hippocampal NR2A/2B subunits related to cognitive impairment in a pristane-induced lupus BALB/c mice. https://doi.org/10.1101/631879

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