Molecular mechanisms for abnormal development of the brain

高等动物中枢神经系统的突触连接在各种干扰（如突触输入中断）下发生改变。虽然突触连接的改变可以在成年动物中引起，但在未成熟动物的脑损伤后，神经元连接的改变比成年动物更明显。这种突触连接可改变性的差异可归因于神经元在脑损伤反应中延长其轴突的能力的差异，神经突促进因子的释放量或轴突生长环境的差异。然而，造成这种差异的确切机制尚未得到澄清。本研究旨在了解早期脑损伤后突触输入重组的分子机制。为此，我们试图培养能够识别生长相关分子的单克隆抗体。由于已经确定猫的感觉运动皮层的早期单侧损伤会引起异常的交叉皮质投影，我们使用含有半脑切除的猫的红色核的大脑匀浆作为抗原。免疫抑制技术也被使用。我们获得了三种特异性染色红核的单克隆抗体。另一种单克隆抗体识别的抗原在生长的脊髓和视神经轴突中短暂表达。生化研究表明抗原是一种糖蛋白。通过本研究获得的单克隆抗体将对进一步了解神经系统发育的分子机制非常有用。

It is well established that synaptic connections in the central nervous system of higher animals are modified following various perturbations such as interruption of synaptic inputs. Although modifications of synaptic connections can be induced in adult animals, more prominent alteration of neuronal connections are seen after brain damage in immature animals than in adults. This difference in modifiability of synaptic connection could be ascribed to difference in capability of neurons to extend their axons in response to brain damage, the amount of neurite promoting factor(s) released by deafferentation or environment for axonal growth. However, the exact mechanims for this difference has not yet been clarified. The present study was carried out in an attempt to gain insight into the molecular mechanisms for reorganization of synatic inputs after early brain damage.For this purpose we attempted to raise monoclonal antibodies which may recognize growth related molecules. Since it has been established that early unilateral damage of the sensorimotor cortex of the kitten gives rise to aberrant crossed corticorubral projection, we used homogenate of the brain containing the red nucleus of hemispherectomized kitten as an antigen.An immuno-suppression technique was also utilized.We have obtained three monoclonal antibodies which specifically stain the red nucleus. Another monoclonal antibody recognized antigen which was transiently expressed in growing axons of the spinal cord and optic nerve. Biochemical studies implicated that the antigen is a glycoprotein. The monoclonal antibodies obtained through this study would be very useful for further understanding molocular mechanisms of development of the nervous system.