Molecular mechanisms for abnormal development of the brain

众所周知，在高等动物的中枢神经系统中，突触连接在各种扰动（如突触输入的中断）后会发生改变。虽然在成年动物中可以诱导突触连接的改变，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显著。突触连接的可修改性的这种差异可以归因于神经元响应于脑损伤而延伸其轴突的能力的差异、由去传入神经释放的轴突促进因子的量或轴突生长的环境。然而，这种差异的确切机制尚未澄清。本研究旨在探讨脑损伤早期突触输入重组的分子机制，并尝试制备可识别生长相关分子的单克隆抗体。由于已证实小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红核投射，我们使用含有大脑半球切除小猫红核的脑匀浆作为抗原，并利用免疫抑制技术，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在脊髓和视神经的生长轴突中瞬时表达的抗原。生物化学研究表明该抗原是一种糖蛋白。通过本研究获得的单克隆抗体将有助于进一步了解神经系统发育的分子机制。

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.