Crino P B, Trojanowski J Q, Eberwine J
Department of Neurology, University of Pennsylvania Medical Center, Philadelphia 19140, USA.
Acta Neuropathol. 1997 Jun;93(6):619-27. doi: 10.1007/s004010050660.
Cortical dysplasias (CD) are characterized histologically by disorganized cortical lamination and abnormally shaped neurons. We hypothesized that neurons within CD have failed to differentiate fully and may express proteins such as cytoskeletal elements characteristic of immature cells. Disrupted expression of certain cytoskeletal proteins, which have been implicated in neuronal polarity, process outgrowth, and migration, could result in disorganized cortical lamination. Thus, we probed two CD subtypes, focal CD (FCD) and hemimegalencephaly (HME), with antibodies specific for cytoskeletal proteins that are developmentally regulated in neural progenitor cells and neurons to define more fully the developmental phenotype of neurons within CD. Microtubule-associated protein 1B (MAP1B) and the intermediate filament (IF) protein nestin are enriched in neural progenitors, whereas MAP2B, phosphorylated and non-phosphorylated forms of medium (NFM) and high (NFH) molecular weight neurofilament (NF) proteins, as well as the light NF subunit (NFL) and IF protein alpha internexin are expressed in developing and mature neurons. Immunolabeling for internexin and MAP1B was more abundant in the most abnormally shaped neurons that populated dysplastic regions than in adjacent regions exhibiting milder cytoarchitectural abnormalities or control cortex. Nestin immunoreactivity was noted in large dysplastic and heterotopic neurons within the deeper cortical layers of CD specimens but not in normal cortex. In contrast, neurons in CD specimens also expressed cytoskeletal markers characteristic of differentiated neurons such as NF subunits and MAP2B. These findings suggest that the cytoarchitectural abnormalities in CD may reflect pathophysiological changes in the developing brain that disrupt expression of several key components of the neuronal cytoskeleton and may contribute to impaired migration of cortical neurons.
皮质发育异常（CD）在组织学上的特征是皮质分层紊乱和神经元形态异常。我们推测，CD内的神经元未能完全分化，可能会表达诸如未成熟细胞特有的细胞骨架成分等蛋白质。某些与神经元极性、突起生长和迁移有关的细胞骨架蛋白表达中断，可能导致皮质分层紊乱。因此，我们用对神经祖细胞和神经元中发育调控的细胞骨架蛋白具有特异性的抗体，对两种CD亚型，即局灶性CD（FCD）和半侧巨脑回（HME）进行检测，以更全面地定义CD内神经元的发育表型。微管相关蛋白1B（MAP1B）和中间丝（IF）蛋白巢蛋白在神经祖细胞中富集，而MAP2B、中等分子量（NFM）和高分子量（NFH）神经丝（NF）蛋白的磷酸化和非磷酸化形式，以及轻链NF亚基（NFL）和IF蛋白α-连接蛋白在发育中和成熟的神经元中表达。在发育异常区域中形状最异常的神经元中，连接蛋白和MAP1B的免疫标记比在表现出较轻细胞结构异常的相邻区域或对照皮质中更为丰富。在CD标本深层皮质层内的大型发育异常和异位神经元中发现了巢蛋白免疫反应性，但在正常皮质中未发现。相反，CD标本中的神经元也表达了分化神经元特有的细胞骨架标记物，如NF亚基和MAP2B。这些发现表明，CD中的细胞结构异常可能反映了发育中大脑的病理生理变化，这些变化破坏了神经元细胞骨架的几个关键成分的表达，并可能导致皮质神经元迁移受损。
