Institute of Neuropathology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Institute of Neuropathology, University Hospital of Zurich, University of Zurich, Schmelzbergstr. 12, 8091, Zurich, Switzerland.
Brain Struct Funct. 2018 Sep;223(7):3463-3471. doi: 10.1007/s00429-018-1699-9. Epub 2018 Jun 23.
The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies, which may trigger vascular thrombosis with consecutive infarcts. However, cognitive dysfunctions representing one of the most commonest neuropsychiatric symptoms are frequently present despite the absence of any ischemic brain lesions. Data on the structural and functional basis of the neuropsychiatric symptoms are sparse. To examine the effect of APS on hippocampal neurogenesis and on white matter, we induced experimental APS (eAPS) in adult female Balb/C mice by immunization with β2-glycoprotein 1. To investigate cell proliferation in the dentate gyrus granular cell layer (DG GCL), eAPS and control mice (n = 5, each) were injected with 5-bromo-2'-deoxyuridine (BrdU) once a day for 10 subsequent days. Sixteen weeks after immunization, eAPS resulted in a significant reduction of BrdU-positive cells in the DG GCL compared to control animals. However, double staining with doublecortin and NeuN revealed a largely preserved neurogenesis. Ultrastructural analysis of corpus callosum (CC) axons in eAPS (n = 6) and control mice (n = 7) revealed no significant changes in CC axon diameter or g-ratio. In conclusion, decreased cellular proliferation in the hippocampus of eAPS mice indicates a limited regenerative potential and may represent one neuropathological substrate of cognitive changes in APS while evidence for alterations of white matter integrity is lacking.
抗磷脂综合征 (APS) 是一种自身免疫性疾病，其特征是存在抗磷脂抗体，这可能会引发血管血栓形成和随后的梗死。然而，尽管没有任何缺血性脑损伤，认知功能障碍作为最常见的神经精神症状之一却经常存在。关于神经精神症状的结构和功能基础的数据很少。为了研究 APS 对海马神经发生和白质的影响，我们通过用β2-糖蛋白 1 免疫成年雌性 Balb/C 小鼠来诱导实验性 APS (eAPS)。为了研究齿状回颗粒细胞层 (DG GCL) 中的细胞增殖，eAPS 和对照小鼠 (n = 5，每组) 每天注射一次 5-溴-2'-脱氧尿苷 (BrdU)，持续 10 天。免疫后 16 周，eAPS 导致 DG GCL 中的 BrdU 阳性细胞显著减少，与对照动物相比。然而，双皮质酮和 NeuN 的双重染色显示神经发生基本保留。eAPS (n = 6) 和对照小鼠 (n = 7) 的胼胝体 (CC) 轴突的超微结构分析显示 CC 轴突直径或 g 比没有显著变化。总之，eAPS 小鼠海马体中细胞增殖减少表明其再生潜力有限，可能是 APS 认知变化的一种神经病理学基础，而白质完整性改变的证据不足。
