title: Mice with experimental antiphospholipid syndrome display hippocampal dysfunction and a reduction of dendritic complexity in hippocampal CA1 neurones.
abstract: OBJECTIVE
  The antiphospholipid syndrome (APS) is an autoimmune disease characterized by high titres of auto-antibodies (aPL) leading to thrombosis and consequent infarcts. However, many affected patients develop neurological symptoms in the absence of stroke. Similarly, in a mouse model of this disease (eAPS), animals consistently develop behavioural abnormalities despite lack of ischemic brain injury. Therefore, the present study was designed to identify structural alterations of hippocampal neurones underlying the neurological symptoms in eAPS.
  
  
  METHODS
  Adult female Balb/C mice were subjected to either induction of eAPS by immunization with β2-Glycoprotein 1 or to a control group. After sixteen weeks animals underwent behavioural and cognitive testing using Staircase test (experiment 1 and 2) and Y-maze alternation test (experiment 1) and were tested for serum aPL levels (both experiments). Animals of experiment 1 (n = 7/group) were used for hippocampal neurone analysis using Golgi-Cox staining. Animals of experiment 2 (n = 7/group) were used to analyse molecular markers of total dendritic integrity (MAP2), presynaptic plasticity (synaptobrevin 2/VAMP2) and dendritic spines (synaptopodin) using immunohistochemistry.
  
  
  RESULTS
  eAPS mice developed increased aPL titres and presented with abnormal behaviour and impaired short term memory. Further, they revealed a reduction of dendritic complexity of hippocampal CA1 neurones as reflected by decreased dendritic length, arborization and spine density, respectively. Additional decrease of the spine-associated protein expression of Synaptopodin points to dendritic spines as major targets in the pathological process.
  
  
  CONCLUSIONS
  Reduction of hippocampal dendritic complexity may represent the structural basis for the behavioural and cognitive abnormalities of eAPS mice.
authors.affiliation: Department of Neuropathology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Frauenknecht
authors.affiliation: Department of Neurology, Chaim Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Hashomer, Israel.
authors.forename: Aviva
authors.initials: A
authors.lastname: Katzav
authors.affiliation: Department of Neurology, Chaim Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Hashomer, Israel.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ronen
authors.initials: R
authors.lastname: Weiss Lavi
authors.affiliation: Department of Neurology, Chaim Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Hashomer, Israel.
authors.forename: Avishag
authors.initials: A
authors.lastname: Sabag
authors.affiliation: Department of Neuropathology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Otten
authors.affiliation: Department of Neurology, Chaim Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Hashomer, Israel.
authors.forename: Joab
authors.initials: J
authors.lastname: Chapman
authors.affiliation: Department of Neuropathology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.|Focus Program Translational Neurosciences (FTN), Rhine Main Neuroscience Network (rmn2), Germany.
authors.forename: Clemens J
authors.initials: CJ
authors.lastname: Sommer
mesh_terms: D000818:Animals; D016736:Antiphospholipid Syndrome / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D001323:Autoantibodies / Q000097:blood; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D049229:Dendritic Spines / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000473:pathology; D009043:Motor Activity; D053482:beta 2-Glycoprotein I
chemical_list: D001323:Autoantibodies; D053482:beta 2-Glycoprotein I
keywords: Golgi-Cox method; antiphospholipid syndrome; behaviour; dendrites; dendritic spines; hippocampus; synaptopodin