Carceller Hector, Rovira-Esteban Laura, Nacher Juan, Castrén Eero, Guirado Ramon
Departamento de Biologia Celular, Spanish National Network for Research in Mental Health, CIBERSAM, Fundación Investigación Hospital Clínico de Valencia, INCLIVA, Universitat de Valencia Valencia Valencia, Spain.
Neuroscience Center, University of Helsinki Helsinki, Finland.
Front Cell Neurosci. 2016 Mar 10;10:65. doi: 10.3389/fncel.2016.00065. eCollection 2016.
Reelin, a glycoprotein expressed by Cajal-Retzius neurons throughout the marginal layer of developing neocortex, has been extensively shown to play an important role during brain development, guiding neuronal migration and detachment from radial glia. During the adult life, however, many studies have associated Reelin expression to enhanced neuronal plasticity. Although its mechanism of action in the adult brain remains mostly unknown, Reelin is expressed mainly by a subset of mature interneurons. Here, we confirm the described phenotype of this subpopulation in the adult neocortex. We show that these mature interneurons, although being in close proximity, lack polysialylated neural cell adhesion molecule (PSA-NCAM) expression, a molecule expressed by a subpopulation of mature interneurons, related to brain development and involved in neuronal plasticity of the adult brain as well. However, in the layer II of Piriform cortex there is a high density of cells expressing Reelin whose neurochemical phenotype and connectivity has not been described before. Interestingly, in close proximity to these Reelin expressing cells there is a numerous subpopulation of immature neurons expressing PSA-NCAM and doublecortin (DCX) in this layer of the Piriform cortex. Here, we show that Reelin cells express the neuronal marker Neuronal Nuclei (NeuN), but however the majority of neurons lack markers of mature excitatory or inhibitory neurons. A detail analysis of its morphology indicates these that some of these cells might correspond to semilunar neurons. Interestingly, we found that the majority of these cells express T-box brain 1 (TBR-1) a transcription factor found not only in post-mitotic neurons that differentiate to glutamatergic excitatory neurons but also in Cajal-Retzius cells. We suggest that the function of these Reelin expressing cells might be similar to that of the Cajal-Retzius cells during development, having a role in the maintenance of the immature phenotype of the PSA-NCAM/DCX neurons through its receptors apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR) in the Piriform cortex layer II during adulthood.
Reelin是一种由Cajal-Retzius神经元在发育中的新皮质边缘层全程表达的糖蛋白，已被广泛证明在脑发育过程中发挥重要作用，引导神经元迁移并使其与放射状胶质细胞分离。然而，在成年期，许多研究将Reelin的表达与增强的神经元可塑性联系起来。尽管其在成人大脑中的作用机制大多仍不清楚，但Reelin主要由一部分成熟的中间神经元表达。在此，我们证实了成体新皮质中这一亚群的上述表型。我们发现，这些成熟的中间神经元尽管彼此相邻，但缺乏多唾液酸神经细胞黏附分子（PSA-NCAM）的表达，PSA-NCAM是由一部分成熟中间神经元表达的一种分子，与脑发育相关且也参与成人大脑的神经元可塑性。然而，在梨状皮质的II层中有高密度表达Reelin的细胞，其神经化学表型和连接性此前尚未被描述。有趣的是，在梨状皮质的这一层中，与这些表达Reelin的细胞紧邻的是大量表达PSA-NCAM和双皮质素（DCX）的未成熟神经元亚群。在此，我们表明表达Reelin的细胞表达神经元标志物神经元细胞核（NeuN），然而大多数神经元缺乏成熟兴奋性或抑制性神经元的标志物。对其形态的详细分析表明，其中一些细胞可能对应于半月形神经元。有趣的是，我们发现这些细胞中的大多数表达T盒脑蛋白1（TBR-1），这是一种不仅在分化为谷氨酸能兴奋性神经元的有丝分裂后神经元中发现，而且在Cajal-Retzius细胞中也发现的转录因子。我们认为，这些表达Reelin的细胞在成年期梨状皮质II层中的功能可能类似于发育过程中的Cajal-Retzius细胞，通过其受体载脂蛋白E受体2（ApoER2）和极低密度脂蛋白受体（VLDLR）在维持PSA-NCAM/DCX神经元的未成熟表型方面发挥作用。
