title: Altered receptor binding densities in experimental antiphospholipid syndrome despite only moderately enhanced autoantibody levels and absence of behavioral features.
abstract: Experimental antiphospholipid syndrome (eAPS) in Balb/c mice causes neuropsychiatric abnormalities including hyperactivity, increased explorative behavior and cognitive deficits. Recently, we have demonstrated that these behavioral changes were linked to an upregulation of serotonergic 5-HT1A receptor binding densities in cortical and hippocampal regions while excitatory and inhibitory neurotransmitter receptors remain largely unchanged. To examine whether the observed behavioral features depend on a critical antibody concentration, mice with only moderately enhanced antiphospholipid antibodies (aPL), about 50-80% of high levels, were analyzed and compared to controls. The staircase test was used to test animals for hyperactivity and explorative behavior. The brains were analyzed for tissue integrity and inflammation. Ligand binding densities of NMDA, AMPA, GABAA, 5-HT1A, M1 and M2 muscarinic acetylcholine receptors, respectively, were analyzed by in vitro receptor autoradiography and compared to brains of mice from our previous study with high levels of aPL. Mice with only moderately enhanced aPL did not develop significant behavioral changes. Brain parenchyma remained intact and neither inflammation nor glial activation was detectable. However, there was a significant decrease of NMDA receptor binding densities in the motor cortex as well as an increase in M1 binding densities in cortical and hippocampal regions, whereas the other receptors analyzed were not altered. Lack of neuropsychiatric symptoms may be due to modulations of receptors resulting in normal behavior. In conclusion, our results support the hypothesis that high levels of aPL are required for the manifestation of neuropsychiatric involvement while at lower antibody levels compensatory mechanisms may preserve normal behavior.
authors: Department of Neuropathology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany. Electronic address: katrin.frauenknecht@unimedizin-mainz.de.
authors: Katrin
authors: K
authors: Frauenknecht
authors: Department of Neurology, Chaim Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 52621 Tel Hashomer, Israel.
authors: Aviva
authors: A
authors: Katzav
authors: Department of Neuropathology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
authors: Christina
authors: C
authors: Grimm
authors: Department of Neurology, Chaim Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 52621 Tel Hashomer, Israel.
authors: Joab
authors: J
authors: Chapman
authors: Department of Neuropathology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
authors: Clemens J
authors: CJ
authors: Sommer
mesh_terms: D000818:Animals; D016736:Antiphospholipid Syndrome / Q000276:immunology* / Q000378:metabolism*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D009483:Neuropsychological Tests; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D017981:Receptors, Neurotransmitter
keywords: 5-HT(1A) receptor; Antiphospholipid antibody level; Antiphospholipid syndrome; Behavior; In vitro receptor autoradiography; Neurotransmitter receptor