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57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie (DGNN)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

12. - 15.09.2012, Erlangen

Banner: 57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie

Neurological Impairment in Experimental Antiphospholipid Syndrome is Associated with increased Ligand Binding to Serotonergic 5-HT1A Receptors

Meeting Abstract

  • presenting/speaker Katrin Frauenknecht - University Medical Center of the Johannes Gutenberg University Mainz, Department of Neuropathology, Mainz, Germany
  • Christina Grimm - University Medical Center of the Johannes Gutenberg University Mainz, Department of Neuropathology, Mainz, Germany
  • Aviva Katzav - Chaim Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Department of Neuropathology, Tel Hashomer, Israel
  • Joab Chapman - Chaim Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Department of Neuropathology, Tel Hashomer, Israel
  • Clemens Sommer - University Medical Center of the Johannes Gutenberg University Mainz, Department of Neuropathology, Mainz, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP2.1

DOI: 10.3205/12dgnn037, URN: urn:nbn:de:0183-12dgnn0373

Veröffentlicht: 11. September 2012

© 2012 Frauenknecht et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

The antiphospholipid syndrome (APS) is an autoimmune disease where the presence of high titers of circulating autoantibodies may cause thrombosis with consecutive infarcts. In mouse models of experimental APS (eAPS), mice develop characteristic clinical manifestations which are very similar to those described for human APS patients including high titers of aPL, thrombosis, and fetal loss. Neurological involvement is also common both in models of eAPS and in APS patients but, apart from stroke and transient ischemic attacks, many of these neurological manifestations cannot be explained by the prothrombotic potential of aPL alone. The morphological and structural data which potentially underlie the behavioral abnormalities are limited. Therefore, we screened brains of eAPS mice with documented neurological symptoms, namely altered spatial memory as well as increased locomotor activity and enhanced exploratory activity (Shrot et al. Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies. Lupus 2002;11:736-43), and control mice immunized with conjugated Freund's adjuvant (CFA) for pathological changes reflecting the molecular basis of these behavioral changes. Infiltrating lymphocytes were characterized using antibodies against CD3, CD4, CD8 and forkhead boxP3 (Foxp3), respectively. Further, 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 using in vitro receptor autoradiography. No significant inflammatory reaction occured in eAPS mice. There was neither activation of astrocytes or microglia nor accumulation of macrophages. Interestingly, there was an increase in receptor ligand binding densities of serotonergic 5-HT1A - in particular in the hippocampus and cortex - whereas changes of excitatory glutamate receptors as well as of inhibitory GABAA-receptors were only marginal. We hypothesize that, apart from its well-known effects in the vascular system, aPL may possess a substantial potential to interact with neurotransmitter receptors in the brain. Therapeutic experiments on this model may offer novel therapeutic optionsvia modulation of the serotonergic system.