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Neurological impairment in experimental antiphospholipid syndrome is associated with increased ligand binding to hippocampal and cortical serotonergic 5-HT1A receptors.
- Source :
-
Immunobiology [Immunobiology] 2013 Apr; Vol. 218 (4), pp. 517-26. Date of Electronic Publication: 2012 Jun 27. - Publication Year :
- 2013
-
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.<br /> (Copyright © 2012 Elsevier GmbH. All rights reserved.)
- Subjects :
- Animals
Antigens, Differentiation biosynthesis
Antigens, Differentiation immunology
Antiphospholipid Syndrome metabolism
Antiphospholipid Syndrome pathology
Astrocytes immunology
Astrocytes metabolism
Astrocytes pathology
Autoantibodies blood
Autoantibodies immunology
Disease Models, Animal
Hippocampus metabolism
Hippocampus pathology
Lymphocytes immunology
Lymphocytes metabolism
Lymphocytes pathology
Macrophages immunology
Macrophages metabolism
Macrophages pathology
Mice
Nervous System Diseases metabolism
Nervous System Diseases pathology
Receptor, Serotonin, 5-HT1A biosynthesis
Somatosensory Cortex metabolism
Somatosensory Cortex pathology
Antiphospholipid Syndrome immunology
Behavior, Animal
Hippocampus immunology
Nervous System Diseases immunology
Receptor, Serotonin, 5-HT1A immunology
Somatosensory Cortex immunology
Up-Regulation immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3279
- Volume :
- 218
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Immunobiology
- Publication Type :
- Academic Journal
- Accession number :
- 22884359
- Full Text :
- https://doi.org/10.1016/j.imbio.2012.06.011