Abnormal olfactory function demonstrated by manganese-enhanced MRI in mice with experimental neuropsychiatric lupus

Shaye Kivity1, Galia Tsarfaty, Nancy Agmon-Levin

  • 1Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Israel.

Insights

Mice with experimental neuropsychiatric lupus (NPSLE) showed depression-like behavior and reduced smell. Manganese-enhanced MRI (MEMRI) revealed impaired olfactory pathways in these mice, confirming a link between NPSLE and olfactory dysfunction.

Area of Science:

  • Neuroscience
  • Immunology
  • Radiology

Background:

  • Experimental neuropsychiatric lupus (NPSLE) in mice, induced by anti-ribosomal-P antibodies, presents with depression-like behavior and olfactory deficits.
  • Manganese-enhanced MRI (MEMRI) is a technique for in vivo mapping of functional neuronal connections, including the olfactory tract.

Purpose of the Study:

  • To investigate the impact of anti-ribosomal-P antibody injection on the olfactory pathway using MEMRI.
  • To correlate behavioral and functional changes in the olfactory system of mice with experimental NPSLE.

Main Methods:

  • Twenty mice were intra-cerebro-ventricularly injected with either human anti-ribosomal-P antibodies (n=10) or human IgG antibodies (control, n=10).
  • Depression-like behavior was assessed using the forced swimming test.
  • Olfactory function was evaluated by menthol concentration testing.
  • MEMRI was employed to visualize and quantify manganese enhancement in the olfactory system.

Main Results:

  • Passive transfer of anti-ribosomal-P antibodies induced depression-like behavior and a significant deficit in olfactory function.
  • MEMRI demonstrated a significant reduction in normalized manganese enhancement ratios within olfactory structures of anti-ribosomal-P treated mice compared to controls (P < 0.001).

Conclusions:

  • Experimental NPSLE, mediated by passive transfer of anti-ribosomal-P antibodies, leads to impaired olfactory neuronal function.
  • MEMRI is effective in demonstrating olfactory pathway dysfunction in a mouse model of depression associated with experimental NPSLE.