Alterations in cell adhesion molecule L1 and functionally related genes in major depression: A postmortem study
Alterations in cell adhesion molecule L1 and functionally related genes in major depression: A postmortem study
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DOI：
10.1016/j.biopsych.2004.12.016
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发表时间：
2005-04-01
影响因子：
10.6
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
背景：目前抑郁症的研究旨在描述在疾病或其治疗中改变的涉及神经元可塑性的基因。我们已经表明抗抑郁药诱导的增加，在三个相互关联的基因，细胞粘附分子L1（CAM-L1），层粘连蛋白，和cAMP反应元件结合蛋白（CREB），和一个相互减少，这些基因随之而来的压力。目前，我们假设，CAM-L1，CREB，和层粘连蛋白可能会改变死后大脑的抑郁subjects.Methods：研究进行了在前额叶和腹顶叶枕叶皮质，59个大脑抑郁症，双相情感障碍，精神分裂症患者，和正常对照组，从斯坦利基金会脑收集。RT-PCR和Western blot分别检测mRNA和蛋白水平。CAM-L1和磷酸化CREB（pCREB）在抑郁组的前额叶皮层中的水平增加，而CAM-L1、层粘连蛋白和pCREB在顶枕皮层中降低。接受抗抑郁药物治疗的抑郁受试者与未接受抗抑郁药物治疗的受试者在顶枕叶皮质中CAM-L1和层粘连蛋白的表达以及在前额叶皮质中pCREB的表达方面存在差异。目前的研究结果表明，在抑郁症和抗抑郁治疗的具体改变，特别是在CAM-L1表明，该基因可能在抑郁症的病理生理和治疗中发挥重要作用。
Background: Current research in depression aims to delineate genes involved in neuronal plasticity that are altered in the disease or its treatment. We have shown antidepressant induced increases in three interrelated genes, cell adhesion molecule L1 (CAM-L1), laminin, and cAMP response element binding protein (CREB), and a reciprocal decrease in these genes consequent to stress. Presently we hypothesized that CAM-L1, CREB, and laminin may be altered in post mortem brains of depressed subjects.Methods: Studies were performed in the prefrontal and in the ventral parieto-occipital cortices, of 59 brains from depressed, bipolar, and schizophrenic subjects, and normal controls, obtained from the Stanley Foundation Brain Collection. mRNA and protein levels were determined by RT-PCR and Western blot analysis, respectively,Results. Levels of CAM-L1 and of phosphorylated CREB (pCREB) were increased in the prefrontal cortex of the depressed group, while CAM-L1, laminin and pCREB were decreased in the parieto-occipital cortex. Depressed subjects receiving antidepressants differed from subjects not receiving antidepressants in the expression of CAM-L1 and laminin in the parieto-occipital cortex, and in the expression of pCREB in the profrontal cortex.Conclusions. The present findings of specific alterations in depression and antidepressant treatment particularly in CAM-L1 suggest that this gene may play an important role in the pathophysiology and treatment of depression.