PAPER Hyperactivity in a mouse model of the antiphospholipid syndrome A Katzav 1 , CG Pick 2 , AD Korczyn 1,3 , E Oest 1 , M Blank 4 , Y Shoenfeld 5 and J Chapman 1,3,5 * 1 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv, Israel; 2 Department of Anatomy, Sackler Faculty of Medicine, Tel Aviv, Israel; 3 Department of Neurology, Sackler Faculty of Medicine, Tel Aviv, Israel; 4 Department of Medicine B and Research Unit of Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Israel; and 5 Department of Biochemistry, Sackler Faculty of Medicine, Tel Aviv, Israel In the antiphospholipid syndrome (APS), antibodies to a complex of phospholipids and beta2- glycoprotein I (b 2 -GPI) are associated with recurrent thromboembolic events, spontaneous abor- tions, thrombocytopenia and central nervous system (CNS) disturbances. Animals immunized with b 2 -GPI develop the systemic manifestations of APS but the involvement of the (CNS) in these animals has not been studied. The objective of the present study was to examine mice with induced experimental APS for behavioral changes. Female Balb=C mice were immunized once with b 2 -GPI in complete Freund's adjuvant (CFA) or with CFA alone. Four months after immunization the mice were tested in the staircase apparatus and the following two variables were measured: (1) number of rears; and (2) number of stairs climbed by the mice. Immunization with b 2 -GPI resulted in elevated levels of circulating anti-negatively charged phospholipids and anti-b 2 -GPI antibodies. The APS mice exhibited hyperactive behavior as re¯ected by more frequent rears (P < 0.023) and higher number of stairs climbed (P < 0.019) by the mice in 3 min. This simple test demonstrated that experimental APS animals are signi®cantly hyperactive and may serve as a marker for CNS involvement in this model. Lupus (2001) 10, 496±499. Keywords: antiphospholipid syndrome; b2-glycoprotein-I (apolipoprotein H); animal model; staircase test; behavior Introduction Antiphospholipid syndrome (APS) is an autoimmune disorder de®ned in patients by occurrence of charac- teristic clinical manifestations including recurrent thromboembolic events (venous or arterial), repeated spontaneous abortions, thrombocytopenia, and the presence of elevated titers of circulating antibodies to negatively-charged phospholipids (aPL), such as anticardiolipin antibodies (aCL), or lupus anticoagu- lant. 1,2 The syndrome can be primary or may be associated with other conditions such as autoimmune disease (most commonly systemic lupus erythemato- sus, SLE). 2,3 A wide spectrum of other clinical manifestations has been reported in association with APS, including valvular heart disease, dermal complications, and neurological disorders involving mainly the central nervous system (CNS). 1,2,4 These neurological com- plications include ischemic events, strokes, seizures, ocular disturbances, dementia, chorea, migraine, trans- verse myelitis and Guillain ± Barre syndrome. 5±8 The pathogenesis of the neurological complications prob- ably involves both ischemic and immune mediated cellular damage but details of these remain to be elucidated. Recent studies show that a 50 kDa serum co-factor, b 2 -glycoprotein I (b 2 -GPI also known as apolipopro- tein H), is required for the binding of pathogenic aPL to phospholipids raised in autoimmune diseases such APS. 9 ± 11 b 2 -GPI-dependent aCL have been shown to be associated with the clinical manifestations of APS in SLE patients, as well as in the primary form of this syndrome. 12 *Correspondence: J Chapman, Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel. E-mail: jchapman@post.tau.ac.il Received 23 October 2000; accepted 22 March 2001 Lupus (2001) 10, 496±499 ß 2001 Arnold All rights reserved 0961±2033 www.arnoldpublishers.com/journals