pro-BDNF在初级感觉神经元内的顺行和逆行输送  

ANTEROGRADE AND RETROGRADE TRANSPORT OF THE PRECURSOR FOR BRAIN- DERIVED NEUROTROPHIC FACTOR IN PRIMARY SENSORY NEURONS

作　　者：王慧[1] 罗学港[1] 鞠躬[2] 

机构地区：[1]中南大学湘雅医学院人体解剖学与神经生物学系,长沙410013 [2]第四军医大学全军神经科学研究所,西安710032

出　　处：《神经解剖学杂志》2005年第1期17-22,共6页Chinese Journal of Neuroanatomy

基　　金：973课题(No. 2003CB515301);湖南省自然科学基金(No. 03JJY3052);教育部重点课题(No. 104141)资助项目

摘　　要：摘　要　研究表明脑源性神经营养因子(BDNF)在神经元内可顺行运输至末梢并释放到下一级神经元参与突触可塑性等功能。而成熟的BDNF由其前体分子(pro -BDNF)经蛋白酶水解形成。体外研究表明pro -BDNF可以激活神经营养因子受体TrkB并导致TrkB的磷酸化,但pro -BDNF在体内的作用目前仍不清楚。本文拟探讨内源性pro -BDNF在周围神经的运输。将大鼠坐骨神经结扎或压榨背根制成模型,动物存活不同时间后取坐骨神经、背根神经节和脊髓进行pro -BDNF免疫组织化学染色检测。结果显示:pro- BDNF免疫阳性产物沉积于坐骨神经和背根损伤处的近侧端和远侧端, 24h达高峰,近侧端可持续达 7d而远侧端可达3d;在坐骨神经的近侧端和远侧端、背根神经节和脊髓可检测到全分子量大小的完整pro -BDNF;在转染pro- BDNF质粒后,PC12细胞内可见pro -BDNF免疫阳性产物分布于胞体和突起。这些结果提示pro- BDNF可以象成熟BDNF一样在感觉神经内顺行和逆行运输,并可由神经元分泌、释放而发挥生理作用。Accumulating evidences indicate that BDNF may be trafficked anterogradely, released and uptaken by second- or third-order target neurons and participate in synaptic plasticity. Precursor for brain-derived neurotrophic factor (pro-BDNF) is proteolytically cleaved to form biologically active mature BDNF. In vitro studies observed that pro-BDNF could activate tyrosine kinase receptor B (TrkB) and mediated TrkB phosphorylation. However, whether pro-BDNF has any biological functions in vivo is not known.To address the question we examined the transport of endogenous pro-BDNF in peripheral nerves by immunocytochemistry. The rat sciatic nerves or dorsal roots were ligated or crushed. After different survival periods, the injured sciatic nerves, dorsal roots and spinal cord were examined. The results showed that pro-BDNF was accumulated at both proximal and distal segments of sciatic nerve and dorsal root. The accumulation peaked at 24 hours after injury and lasted at least 7 days at proximal segment and 3 days at the distal part. Pro-BDNF was also detected in the cytoplasm and neurites of the PC12 cells transfected with the pro-BDNF-EGFP plasmid. These studies demonstrate that pro-BDNF, like mature BDNF, is anterogradely and retrogradely transported in the sensory nerves, and that pro-BDNF may be produced and released by neurons and play physiological roles in sensory nerves.

关 键 词：BDNF 坐骨神经 免疫阳性 逆行 脊髓 背根神经节 感觉神经元 突触可塑性 磷酸化 质粒 

分 类 号：Q42[生物学—神经生物学]