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

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.ObjectiveTo 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.MethodsFifty-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.ResultsPristane 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.ConclusionDownregulation 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.

Potential antidepressant effects of Traditional Chinese botanical drug formula Chaihu-Shugan-San and its active ingredients

“…NMDAR is considered a necessary condition for dendritic spine structural remodeling and is believed to be the cellular basis of learning and memory (Matsuzaki et al, 2004). Downregulation of hippocampal NR2A/NR2B has been associated with cognitive impairment (Luciano-Jaramillo et al, 2019). According to the NMDAR signaling pathway, TrkB is rapidly and persistently activated, serving as a crucial binding partner for BDNF in various forms of synaptic plasticity.…”