Barbeau D, Liang J J, Robitalille Y, Quirion R, Srivastava L K
Douglas Hospital Research Centre, McGill University, Montreal, PQ, Canada.
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2785-9. doi: 10.1073/pnas.92.7.2785.
The regulated expression of neural cell adhesion molecule (NCAM) isoforms in the brain is critical for many neurodevelopmental processes including neurulation, axonal outgrowth, and the establishment of neuronal connectivity. We have investigated the expression of the major adult isoforms of NCAM (NCAM-180, NCAM-140, and NCAM-120) and its embryonic highly polysialylated isoform (PSA-NCAM) in the hippocampal region of postmortem brains from 10 schizophrenic and 11 control individuals. Immunohistochemical analysis with a monoclonal antibody recognizing the PSA-NCAM revealed immunoreactivity primarily in the dentate gyrus and in a subset of cells in the hilus region. We have observed a 20-95% reduction in the number of hilar PSA-NCAM-immunoreactive cells in the great majority of schizophrenic brains. The change in PSA-NCAM immunoreactivity is not obvious in other hippocampal subfields. Western blots of tissues from the hippocampal region (as well as from the frontal cortex) probed with a polyclonal antibody recognizing all NCAM isoforms did not reveal significant changes in the overall expression of NCAM, suggesting that the decrease in PSA-NCAM-immunoreactive cells may be related to post-translational processing of the molecule. The expression of this embryonic form of NCAM has been proposed to be related to synaptic rearrangement and plasticity. Therefore, the decrease in PSA-NCAM immunoreactivity in schizophrenic hippocampi may suggest an altered plasticity of this structure in a large proportion of schizophrenic brains. These findings may bear significance to the "neurodevelopmental hypothesis" of schizophrenia.
神经细胞黏附分子（NCAM）亚型在大脑中的调控表达对于包括神经胚形成、轴突生长以及神经元连接建立在内的许多神经发育过程至关重要。我们研究了10名精神分裂症患者和11名对照个体死后大脑海马区中NCAM的主要成人亚型（NCAM - 180、NCAM - 140和NCAM - 120）及其胚胎期高度多聚唾液酸化亚型（PSA - NCAM）的表达。用识别PSA - NCAM的单克隆抗体进行免疫组织化学分析显示，免疫反应主要出现在齿状回和海马回区域的一部分细胞中。我们观察到，在绝大多数精神分裂症患者的大脑中，海马回中PSA - NCAM免疫反应性细胞数量减少了20% - 95%。在海马体的其他亚区，PSA - NCAM免疫反应性的变化并不明显。用识别所有NCAM亚型的多克隆抗体对海马区（以及额叶皮质）组织进行蛋白质免疫印迹分析，未发现NCAM总体表达有显著变化，这表明PSA - NCAM免疫反应性细胞的减少可能与该分子的翻译后加工有关。有人提出这种胚胎形式的NCAM的表达与突触重排和可塑性有关。因此，精神分裂症患者海马体中PSA - NCAM免疫反应性的降低可能表明在很大一部分精神分裂症患者的大脑中，该结构的可塑性发生了改变。这些发现可能对精神分裂症的“神经发育假说”具有重要意义。
