IgG accumulates in inhibitory hippocampal neurons of experimental antiphospholipid syndrome

Aviva Katzav*, Assaf Menachem, Nicola Maggio, Lea Pollak, Chaim G. Pick, Joab Chapman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Mice immunized with β2-glycoprotein I (β2GPI) are an experimental model of the antiphospholipid syndrome (eAPS) displaying elevated titers of antiphospholipid antibodies (aPL). We presently studied whether the behavioral hyperactivity in eAPS mice is associated with invivo binding and accumulation of IgG in the brain. At 6 weeks post immunization eAPS mice had significantly higher levels of aPL (1.32±0.28 and 0.02±0.01 AU, p<0.001 by t-test) compared to adjuvant immunized controls, as measured by ELISA. Significant hyperactivity in a staircase test in the eAPS mice compared to controls was found in stair-climbing (18.4±0.9 and 12.0±1.7, respectively) and rearing measures (23.5±2.1 and 12.5±1.9, p<0.01 by t-test). Immunofluorescence staining in eAPS mice revealed significant invivo accumulation of IgG in cortical and hippocampal neurons which was not seen in controls. Staining for IgG was markedly intense in inhibitory interneurons co-stained for GAD67 in the hippocampus of eAPS mice. The integrity of the blood brain barrier (BBB) evaluated by injection of Evans blue (EB) was impaired in eAPS and adjuvant immunized mice compared to naïve mice. Electrophysiological recordings in hippocampal brain slices showed altered response to paired pulse stimulation as well as dysregulation of carbachol-induced γ- oscillations in eAPS mice compared to control. Penetration into the brain and direct interaction of aPL with inhibitory interneurons in the hippocampus may explain the hyperactive behavior of the eAPS mice. A direct role of aPL in causing CNS dysfunction points to these antibodies as an important therapeutic target in APS.

Original languageEnglish
Pages (from-to)86-93
Number of pages8
JournalJournal of Autoimmunity
Volume55
Issue number1
DOIs
StatePublished - Dec 2014

Funding

FundersFunder number
Israel Science Foundation917/08

    Keywords

    • Antiphospholipid antibodies
    • Blood brain barrier
    • Experimental antiphospholipid syndrome
    • Hippocampus
    • Hyperactivity
    • Inhibitory interneurons

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