CELL ADHESION MOLECULES--ABNORMALITIES IN NEUROPSYCHIATRIC DISORDERS

细胞之间的相互作用指导着中枢神经系统的发育，就像 所有器官系统。CNS的最终形式和组织取决于 细胞之间的这些相互作用；这些相互作用依次 依赖于一些特定类别的分子，最重要的是 其中包括细胞识别分子(CRM)。在成熟的中枢神经系统中， 对于细胞之间的相互作用，CRM仍然至关重要，如在 例如，突触形成、轴突延伸、相互作用 神经元和胶质细胞，细胞对损伤的反应，以及许多其他细胞 事件。我们正在探索客户关系管理中的异常情况的可能性 功能与神经精神疾病有关，尤其是 可能具有发育成分的疾病。两个特别之处 脑脊液中的N-CAM和L1抗原分子异常 精神分裂症患者。这些差异似乎并不代表 一种药物效应。此外，这些异常出现在一种特定的 模式，异常表现在每个模式的特定形式中 分子：N-CAM的120kD形式在 精神分裂症患者，而L1抗原140kD形式减少 达到了类似的程度。同样，N-CAM中的变化虽然较小，但 也见于双相情感障碍患者。TGFs的异常， 在一些系统中调节CRM的表达，似乎不是 造成这些差异的原因：TGFbeta2被发现增加 在包括阿尔茨海默病在内的几种退行性疾病中， 帕金森氏症和多发性硬化症，但不是精神分裂症。 动物研究表明，N-CAM和L1的表达在 因损伤而去传入的大脑区域，外源性L1可以 促进多巴胺能神经元的可塑性。这些数据表明 CRM在神经精神障碍中的潜在作用。

Cell-cell interactions guide development of the CNS, as is the case for all organ systems. The final form and organization of the CNS depends on these interactions between cells; these interactions are in turn dependent upon a number of specific classes of molecules, and foremost among them are 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, interactions between neurons and glia, cellular responses to injury, and many other cellular events. 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, though smaller, changes in N-CAM are also seen in patients withbipolar mood disorder. Abnormalities in TGFs, which in some systems regulate expression of CRMs, do not appear to be responsible for these differences: TGFbeta2 was found to be increased in several degenerative disorders including Alzheimer's disease, Parkinson's disease, and multiple sclerosis, 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 potential role of CRMs in neuropsychiatric disorders.