Lupus-prone B6.Nba2 Male and Female Mice Display Anti-DWEYS Reactivity and a Neuropsychiatric Phenotype

Overview

Journal Brain Behav Immun

Publisher Elsevier

Specialties Allergy & Immunology
Neurology
Psychiatry

Date 2021 Feb 19

PMID 33607233

Citations 4

Authors

Kim Browne

Emily Zhang

James K Sullivan

Kirsten S Evonuk

Tara M DeSilva

Trine N Jorgensen

Affiliations

Soon will be listed here.

Abstract

Objective: Neuropsychiatric lupus (NPSLE), a manifestation of the autoimmune disease systemic lupus erythematosus (SLE), is characterized by psychiatric symptoms including anxiety and depression and upregulated autoantibodies. The B6.Nba2 spontaneous mouse model develops SLE, but has not previously been tested for NPSLE.

Methods: We investigated the NPSLE phenotype in male and female B6.Nba2 mice (n = 12 each) and age- and sex-matched B6 controls (n = 10 each) via behavioral assessments for anxiety, depression, and memory deficits. Serum anti-dsDNA, anti-nRNP, anti-DWEYS peptide reactive IgG autoantibody levels and soluble TWEAK levels were determined by ELISA. Hippocampal regions were stained for activated microglia and neurons.

Results: Both male and female B6.Nba2 mice showed elevated anti-dsDNA IgG, anti-nRNP IgG and anti-DWEYS reactive antibodies, elevated serum soluble TWEAK levels, and a strong anxiety and depression phenotype (p < 0.05-0.0001). Male B6.Nba2 mice developed this phenotype at a slightly older age than females. Female B6.Nba2 mice displayed reduced numbers of neurons in the hippocampal region compared to female B6 controls (p < 0.05).

Conclusion: The B6.Nba2 mouse model recapitulates many known NPSLE phenotypes, making it a promising model to investigate the development of NPSLE in the context of SLE.

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