Molecular mechanisms for abnormal development of the brain

众所周知，高等动物中枢神经系统中的突触连接在受到各种扰动后会发生改变，例如突触输入中断。虽然可以在成年动物身上诱导突触连接的修改，但在未成熟动物的脑损伤后，神经元连接的变化比成年动物更明显。这种突触联系可变性的差异可能归因于神经元对脑损伤反应轴突的能力、去传入释放的轴突促进因子(S)的量或轴突生长环境的不同。然而，这种差异的确切机制还没有弄清楚。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，我们试图制备可识别生长相关分子的单抗。由于已证实猫早期一侧感觉运动皮质的损伤会引起异常的交叉皮质-黑质投射，因此我们以去半球猫红核的脑匀浆为抗原，并利用免疫抑制技术，获得了三种能对红核进行特异性染色的单抗。另一种识别抗原的单抗在脊髓和视神经的生长轴突中瞬时表达。生化研究表明，该抗原是一种糖蛋白。通过本研究获得的单抗将对进一步了解神经系统发育的多眼机制非常有用。

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.