EFFECTS OF ANTIMITOTIC DRUGS ON CNS REGENERATION

拟议研究的目的是调查以下可能性： 病变部位的反应性非神经元细胞可以吞噬生长 轴突和它们的生长锥，因为它们试图穿过病变。 的 模型系统的使用将形成和维护明显的 多聚赖氨酸包被的珠子上的突触前元件。 明显的突触前 在小脑的培养物中， 具有40 nm囊泡和在膜处累积的密度的囊泡 与珠接触。 明显的突触前成分似乎是 被非神经元细胞从珠子上移除，但初步结果显示， 这种作用被抗有丝分裂药物抑制， 师. 这项拟议中的研究将检查抗有丝分裂的效果， 药物对体外和体内表观突触前元件存活的影响 vivo. 第一项研究（I）是在体外进行的，将检查 不同的抗有丝分裂药物对表观突触前元件存活的影响。 在本节中，其他实验将使用免疫细胞化学， 识别在珠子上生长的非神经元细胞类型。 的 第二项研究（II）是在体内进行的，将检查抗有丝分裂的作用， 药物对3-4日龄突触前成分形成的影响 大鼠 初步结果表明，小脑神经元的3-4天， 老年大鼠在植入的珠子上确实形成了明显的突触前元件。 的 这些明显的突触前元件的维持和 将评估抗有丝分裂药物对其存活率的影响。 最后一组 (III)实验将检查成年小脑神经元的反应， 和抗有丝分裂药物对表观 突触前元件存活。 拟议的研究提供了一种新的方法， 对损伤部位再生的理解。 是吞噬细胞 中枢神经系统损伤部位的一些非神经元细胞的反应可能 参与了轴突再生的抑制

The object of the proposed research is to investigate the possibility that reactive non-neuronal cells at the site of a lesion can phagocytose growing axons and their growth cones as they attempt to cross the lesion. The model system used will be the formation and maintenance of apparent presynaptic elements on polylysine coated beads. The apparent presynaptic elements have been shown in cultures of the cerebellum to be neuronal swellings with 40 nm vesicles and with a density acumulated at the membrane in contact with the bead. The apparent presynaptic elements appear to be removed from the beads by non-neuronal cells, but preliminary results show this effect is inhibited by antimitotic drugs which stop non-neuronal cell division. The proposed research will examine the effect of antimitotic drugs on survival of apparent presynaptic elements both in vitro and in vivo. The first studies (I) are in vitro and will examine the effect of different antimitotic drugs on survival of apparent presynaptic elements. In this section additional experiments will use immunocytochemistry to identify the non-neuronal cell types that grow up onto the beads. The second studies (II) are in vivo and will examine the effect of antimitotic drugs on the formation of apparent presynaptic elements in 3-4 day old rats. Preliminary results show that neurons in the cerebellum of 3-4 day old rats do form apparent presynaptic elements on implanted beads. The maintenance of these apparent presynaptic elements and the effect of antimitotic drugs on their survival will be evaluated. The last group (III) of experiments will examine the response of adult cerebellar neurons to polylysine coated beads and the effect of antimitotic drugs on apparent presynaptic element survival. The proposed studies offer a new approach to the understanding of regeneration at the site of lesion. Is the phagocytic response of some non-neuronal cells at the site of CNS lesion possibly involved in the inhibition of axonal regeneration?