CELL ADHESION MOLECULES--ABNORMALITIES IN NEUROPSYCHIATRIC DISORDERS

中枢神经系统的最终形式和组织取决于相互作用 细胞之间的相互作用；这些相互作用取决于许多特定的 分子的类别，其中最重要的是细胞识别 分子(CRM)。在成熟的CNS中，CRM继续对 细胞之间的相互作用，例如，突触形成、轴突 延伸，以及神经元和胶质细胞之间的相互作用。我们正在探索 涉及客户关系管理功能异常的可能性 神经精神疾病，尤指那些可能有 发展的组成部分。两个特殊的分子，N-CAM和L1抗原， 在精神分裂症患者的脑脊液中是异常的。这个 差异似乎并不代表药物效应。此外， 异常是以特定的模式存在的，其中异常 以每个分子的特定形式出现：N-CAM的120kD形式 在精神分裂症患者中增加了大约两倍，而140 kD L1抗原的形式也有类似程度的下降。同样，尽管 躁郁症患者的N-CAM也有较小的变化 无序。脑脊液的这些变化反映在脑脊液的异常 死后海马区组织中可溶性N-CAM的表达 取自人类病人的样本。TGFbetas的异常，在某些情况下 系统调节CRM的表达，似乎不负责 这些差异：在帕金森氏症患者中发现TGFbeta2增加 疾病，但不是精神分裂症。动物研究表明 N-CAM和L1在以下脑区的表达发生变化 外源性L1可促进脊髓的可塑性。 多巴胺能神经突起。这些数据表明，CRM可能在 神经精神障碍。

The final form and organization of the CNS depends on interactions between cells; these interactions are dependent upon a number of specific classes of molecules, foremost among them being the cell recognition molecules (CRMs). In the mature CNS, CRMs continue to be crucial for interactions between cells as in, for example, synapse formation, neurite extension, and interactions between neurons and glia. We are exploring the possibility that abnormalities in CRM functions are involved in neuropsychiatric disease, especially those disorders which may have a developmental component. Two particular molecules, N-CAM and L1 antigen, are abnormal in the cerebrospinal fluid of schizophrenic patients. The differences do not appear to represent a drug effect. Moreover, the abnormalities are present in a specific pattern, with the abnormality being seen in certain forms of each molecule: The 120 kD form of N-CAM is increased about two-fold in schizophrenic patients, while the 140 kD form of L1 antigen is decreased to a similar degree. Similarly, although smaller, changes in N-CAM are also seen in patients with bipolar mood disorder. These changes in CSF are reflected in abnormalities of expression of soluble N-CAM in hippocampal tissue from post-mortem samples from human patients. Abnormalities in TGFbetas, which in some systems regulate expression of CRMs, do not appear to be responsible for these differences: TGFbeta2 was found to be increased in Parkinson's disease, but not in schizophrenia. Animal studies suggest that expression of N-CAM and L1 is altered in brain areas that are deafferented by injury, and that exogenous L1 can promote plasticity of dopaminergic neurites. These data suggest a possible role of CRMs in neuropsychiatric disorders.