Abnormal olfactory function demonstrated by manganese-enhanced MRI in mice with experimental neuropsychiatric lupus.
Mice with experimental neuropsychiatric lupus (NPSLE), induced by anti-ribosomal-P antibodies, developed depression-like behavior and a diminished sense of smell. Manganese-enhanced MRI (MEMRI) allows in vivo mapping of functional neuronal connections in the brain, including the olfactory tract. The aim of this study was to analyze and describe, via the MEMRI technique, the effect of the anti-ribosomal-P injection on the olfactory pathway. Twenty mice were intra-cerebra-ventricular injected to the right hemisphere: 10 with human anti-ribosomal-P antibodies and 10 with human IgG antibodies (control). Depression was addressed by forced swimming test and smell function was evaluated by smelling different concentrations of menthol. MEMRI was used to investigate the olfactory system in these mice. Passive transfer of anti-ribosomal-P to mice resulted in a depression-like behavior, accompanied with a significant deficit in olfactory function. MEMRI of these mice demonstrated significant reduction (P < 0.001) in normalized manganese enhancement ratios of olfactory structures, compared to control mice. We concluded that an impaired olfactory neuronal function in mice with experimental depression, mediated by passive transfer of human-anti-ribosomal-P, can be demonstrated by MEMRI.
Kivity
Shaye
S
Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Tsarfaty
Galia
G
Agmon-Levin
Nancy
N
Blank
Miri
M
Manor
David
D
Konen
Eli
E
Chapman
Joab
J
Reichlin
Morris
M
Wasson
Craig
C
Shoenfeld
Yehuda
Y
Kushnir
Tammar
T
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D003863:Depression / Q000209:etiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007089:Image Enhancement; D007276:Injections, Intraventricular; D020945:Lupus Vasculitis, Central Nervous System / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese / Q000502:physiology*; D008610:Menthol / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D009833:Olfactory Pathways / Q000502:physiology*; D012269:Ribosomal Proteins / Q000008:administration & dosage / Q000276:immunology; D012903:Smell / Q000502:physiology
D001323:Autoantibodies; D012269:Ribosomal Proteins; D008610:Menthol; D008345:Manganese