Cyclic AMP elevates tubulin expression without increasing intrinsic axon growth capacity

Cyclic AMP elevates tubulin expression without increasing intrinsic axon growth capacity
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DOI:
10.1016/j.expneurol.2004.03.010
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发表时间:
2004-10-01
影响因子:
5.3
通讯作者:
Hoffman, PN
Hoffman, PN
中科院分区:
医学2区
文献类型:
--
作者:
Han, PJ;Shukla, S;Hoffman, PN

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将大鼠背根神经节(DRG)神经元暴露于二丁酰cAMP(db-cAMP),通过消除CNS髓鞘抑制伸长的能力,使脊髓中的中央分支再生。条件性损伤(CL)通过增加神经元cAMP水平促进脊髓中中央分支的类似再生。这是一个猜测是否CL的任何其他影响是由升高的cAMP触发的问题。我们发现,像CL一样,神经节内注射db-cAMP增加了生长相关微管蛋白同种型的表达。然而,与CL不同,db-cAMP不增加微管蛋白通过慢组分B(SC B)递送至生长轴突的尖端的速度。db-cAMP也不能充分增加内在轴突生长能力以提高坐骨神经中外周分支的再生速率或使中央分支能够在不含所有CNS伸长抑制剂的环境中伸长长距离(即,外周神经移植物在脊柱横断部位移植到脊髓中)。因此,由CL诱导的cAMP增加诱导了一些但不是全部的变化,这些变化可能是增加内在轴突生长能力所必需的。(C)2004年爱思唯尔公司All rights reserved.
Exposing rat dorsal root ganglion (DRG) neurons to dibutyryl cAMP (db-cAMP) enables central branches to regenerate in the spinal cord by nullifying the ability of CNS myelin to inhibit elongation. A conditioning lesion (CL) promotes similar regeneration of central branches in the spinal cord by increasing neuronal cAMP levels. It is a matter of speculation whether any of the other effects of a CL are triggered by elevated cAMP. We found that like a CL, intraganglionic injection of db-cAMP increases the expression of growth-associated tubulin isotypes. However, unlike a CL, db-cAMP does not increase the velocity at which tubulin is delivered to the tips of growing axons by slow component b (SCb). db-cAMP also fails to increase intrinsic axon growth capacity enough to raise the rate of regeneration of peripheral branches in the sciatic nerve or enable central branches to elongate long distances in an environment free of all CNS inhibitors of elongation (i.e., a peripheral nerve graft transplanted into the spinal cord at the site of dorsal column transection). Thus, the increase in cAMP induced by a CL induces some, but not all, of the changes that may be necessary to increase intrinsic axon growth capacity. (C) 2004 Elsevier Inc. All rights reserved.