Antidepressants and prolonged stress in rats modulate CAM-L1, laminin, and pCREB, implicated in neuronal plasticity
Antidepressants and prolonged stress in rats modulate CAM-L1, laminin, and pCREB, implicated in neuronal plasticity
复制标题
DOI：
10.1016/j.nbd.2005.03.023
复制
发表时间：
2005-11-01
影响因子：
6.1
通讯作者：
Ben-Shachar, D
中科院分区：
文献类型：
--
作者：
Laifenfeld, D;Karry, R;Ben-Shachar, D
之前，我们报道了NE促进神经母细胞瘤细胞可塑性过程的能力，通过形态学变化观察到，如细长的富含颗粒的细胞体和神经新生，以及多能性标记物Oct4的逐渐减少和生长锥标记物GAP-43的增加。这伴随着三个可塑性基因的诱导，形成一个功能簇，细胞粘附分子L1 (CAM-L1)，层粘连蛋白和CREB，都参与神经元的可塑性和神经突的生长。在本研究中，我们假设NE对CAM-L1、层粘连蛋白和CREB/pCREB的调节可以介导抗抑郁药作用模式的可塑性过程，以及大鼠应激的长期影响，因为这两者都与NE改变和神经元可塑性有关。在第一个实验中，大鼠长期服用抗抑郁药（21天）。在第二个实验中，大鼠暴露于慢性压力下，并在4个月后进行检查，该模型显示出压力的行为指标。我们发现，在长期使用去甲肾上腺素能抗抑郁药地西帕明治疗的大鼠中，以及在较小程度上使用氟西汀治疗的大鼠中，CAM-L1、层联蛋白和pCREB的mRNA和蛋白质水平发生了脑区域特异性改变。应激大鼠表现出CAM-L1、层粘连蛋白和pCREB的减少，特别是在与应激有关的大脑区域。我们的研究结果表明，去甲肾上腺素能调节的可塑性基因，如CAM-L1、层粘连蛋白和CREB，在应激和抑郁症治疗中都起着重要作用。(c) 2005爱思唯尔公司版权所有。
Previously, we reported an ability of NE to promote processes of plasticity in neuroblastoma cells, as observed by morphological changes such as an elongated granule-rich cell body and neuritegenesis, in addition to a progressive decrease in the pluripotent marker Oct4 and an increase in the growth cone marker GAP-43. This was accompanied by the induction of three plasticity genes forming a functional cluster, the cell adhesion molecule L1 (CAM-L1), laminin, and CREB, all involved in neuronal plasticity and neurite outgrowth. In the present study, we hypothesized that the regulation of CAM-L1, laminin, and CREB/pCREB by NE could mediate processes of plasticity in the mode of action of antidepressants, as well as in the long-term effects of stress, in rats, given the association of both with NE alterations and neuronal plasticity. In the first experiment, rats were chronically administered with antidepressants (21 days). In the second experiment, rats were exposed to chronic stress and examined 4 months later, a model shown to exhibit behavioral indices of stress. We found brain region-specific alterations in mRNA and protein levels of CAM-L1, laminin, and pCREB in rats chronically treated with the noradrenergic antidepressant desipramine and, to a lesser extent, in those treated with fluoxetine. Stressed rats presented a decrease in CAM-L1, laminin, and pCREB, specifically in brain areas implicated in stress. Our findings suggest that noradrenergic-regulated plasticity genes such as CAM-L1, laminin, and CREB play an important role both in stress and in the treatment of depression. (c) 2005 Elsevier Inc. All rights reserved.