Ringstedt T, Linnarsson S, Wagner J, Lendahl U, Kokaia Z, Arenas E, Ernfors P, Ibáñez C F
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Neuron. 1998 Aug;21(2):305-15. doi: 10.1016/s0896-6273(00)80540-1.
Cajal-Retzius (CR) cells of the cerebral cortex express receptors for the neurotrophin brain-derived neurotrophic factor (BDNF) and downregulate expression of the extracellular matrix protein Reelin during early postnatal development, coincident with the onset of cortical BDNF expression. During this period, mice lacking BDNF have elevated levels of Reelin in CR cells. Acute BDNF stimulation of cortical neuron cultures and overexpression of BDNF in the developing brain of transgenic mice prior to the onset of endogenous production causes a profound, dose-dependent reduction of Reelin expression in CR cells. In addition, overexpression of BDNF produces gaps and heterotopias in the marginal zone and disorganization and aggregation of cortical CR cells and induces several other malformations, including aberrant cortical lamination, similar to the phenotype of reeler mutant mice, which lack Reelin. These results demonstrate a role for BDNF on cortical CR cells and identify Reelin as a direct effector of this neurotrophin during brain development.
大脑皮层的卡哈尔-雷茨（Cajal-Retzius，CR）细胞表达神经营养蛋白脑源性神经营养因子（BDNF）的受体，并在出生后早期发育过程中下调细胞外基质蛋白Reelin的表达，这与皮层BDNF表达的开始时间一致。在此期间，缺乏BDNF的小鼠CR细胞中Reelin水平升高。在内源性BDNF产生之前，对皮层神经元培养物进行急性BDNF刺激以及在转基因小鼠发育中的大脑中过表达BDNF，会导致CR细胞中Reelin表达出现显著的剂量依赖性降低。此外，BDNF的过表达会在边缘区产生间隙和异位，导致皮层CR细胞紊乱和聚集，并诱发其他几种畸形，包括异常的皮层分层，类似于缺乏Reelin的reeler突变小鼠的表型。这些结果证明了BDNF对皮层CR细胞的作用，并确定Reelin是这种神经营养因子在大脑发育过程中的直接效应物。
