title: Neurological impairment in experimental antiphospholipid syndrome is associated with increased ligand binding to hippocampal and cortical serotonergic 5-HT1A receptors.
abstract: The antiphospholipid syndrome (APS) is an autoimmune disease where the presence of high titers of circulating autoantibodies causes thrombosis with consecutive infarcts. In experimental APS (eAPS), a mouse model of APS, behavioral abnormalities develop in the absence of vessel occlusion or infarcts. Using brain hemispheres of control and eAPS mice with documented neurological and cognitive deficits, we checked for lymphocytic infiltration, activation of glia and macrophages, as well as alterations of ligand binding densities of various neurotransmitter receptors to unravel the molecular basis of this abnormal behavior. Lymphocytic infiltrates were immunohistochemically characterized using antibodies against CD3, CD4, CD8 and forkhead box P3 (Foxp3), respectively. GFAP, Iba1 and CD68-immunohistochemistry was performed, to check for activation of astrocytes, microglia and macrophages. Ligand binding densities of NMDA, AMPA, GABAA and 5-HT1A receptors were analyzed by in vitro receptor autoradiography. No significant inflammatory reaction occurred in eAPS mice. There was neither activation of astrocytes or microglia nor accumulation of macrophages. Binding values of excitatory and inhibitory neurotransmitter receptors were largely unchanged. However, ligand binding densities of the modulatory serotonergic 5-HT1A receptors in the hippocampus and in the primary somatosensory cortex of eAPS mice were significantly upregulated which is suggested to induce the behavioral abnormalities observed.
authors.affiliation: Department of Neuropathology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany. katrin.frauenknecht@unimedizin-mainz.de
authors.forename: Katrin
authors.initials: K
authors.lastname: Frauenknecht
authors.forename: Aviva
authors.initials: A
authors.lastname: Katzav
authors.forename: Christina
authors.initials: C
authors.lastname: Grimm
authors.forename: Joab
authors.initials: J
authors.lastname: Chapman
authors.forename: Clemens J
authors.initials: CJ
authors.lastname: Sommer
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001522:Behavior, Animal; D004195:Disease Models, Animal; D006624:Hippocampus / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009422:Nervous System Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D044282:Receptor, Serotonin, 5-HT1A / Q000096:biosynthesis / Q000276:immunology*; D013003:Somatosensory Cortex / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D000943:Antigens, Differentiation; D001323:Autoantibodies; D044282:Receptor, Serotonin, 5-HT1A