CELL ADHESION MOLECULES--ABNORMALITIES IN NEUROPSYCHIATRIC DISORDERS

CNS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一些特定的 其中最重要的是细胞识别 分子（CRM）。 在成熟的中枢神经系统，CRM仍然是至关重要的， 细胞之间的相互作用，例如，突触的形成，神经突 延伸，以及神经元和神经胶质之间的相互作用。 我们正在探索 CRM功能异常的可能性涉及 神经精神疾病，特别是那些可能具有 发展的组成部分。 两种特殊的分子N-CAM和L1抗原 在精神分裂症患者的脑脊液中是异常的。 的 差异似乎不代表药物作用。 而且 异常以特定模式存在，异常 在每个分子的某些形式中可以看到：N-CAM的120 kD形式 在精神分裂症患者中增加了约两倍，而140 kD L1抗原的形式减少到类似的程度。 同样，虽然 在双相情感患者中，N-CAM的变化也较小 disorder. CSF中的这些变化反映在 死后海马组织可溶性N-CAM的表达 人类患者的样本。 在某些情况下， 系统调节CRM的表达，似乎不负责 这些差异：发现TGF β 2在帕金森氏症患者中增加， 但不是精神分裂症。 动物研究表明， N-CAM和L1的表达在大脑区域发生改变， 外源性L1能促进神经元的可塑性， 多巴胺能神经突 这些数据表明CRM在以下方面可能发挥的作用： 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.