CONTINUOUS INFUSION OF NERVE GROWTH-FACTOR PREVENTS BASAL FOREBRAIN NEURONAL DEATH AFTER FIMBRIA FORNIX TRANSECTION
CONTINUOUS INFUSION OF NERVE GROWTH-FACTOR PREVENTS BASAL FOREBRAIN NEURONAL DEATH AFTER FIMBRIA FORNIX TRANSECTION
复制标题
DOI：
10.1073/pnas.83.23.9231
复制
发表时间：
1986-12-01
影响因子：
11.1
通讯作者：
GAGE, FH
中科院分区：
文献类型：
--
作者：
WILLIAMS, LR;VARON, S;GAGE, FH
通过抽吸同侧穹窿海马伞和胼胝体上纹，切断大鼠内侧隔（MS）和Broca斜角带（VDB）的垂直分支至海马的背侧投射，使其神经元发生快速而严重的细胞死亡。切断后2周，MS的神经元丢失程度为50%的总神经元和70%的胆碱能神经元，VDB的神经元丢失程度为30%的总神经元和40%的胆碱能神经元。我们假设，（i）死亡是由于一个海马源性神经营养因子的损失，和（ii）外源性神经生长因子（NGF）可能提供营养支持的MS/VDB胆碱能神经元，鉴于最近的报道，隔斜角带胆碱能神经元对NGF的反应和NGF的存在，并在海马中产生。在本研究中，我们试图通过脑室内插管装置连续输注外源性7S NGF（1 μ g/周）来防止横断诱导的神经元死亡。我们在这里报告，神经生长因子治疗显着减少总的神经元和胆碱能神经元死亡后2周穹窿海马伞横切;有一个保留的50%的神经元在MS和基本上100%的那些在VDB，否则会死亡。我们的结论是，神经生长因子也有一个非胆碱能神经元的保护作用，因为计算表明，80%的神经生长因子影响的神经元是非胆碱能。
Neurons in the rat medial septum (MS) and vertical limb of the diagonal band of Broca (VDB) undergo a rapid and severe cell death after transection of their dorsal projection to the hippocampus by aspiration of the ipsilateral fimbria fornix and supracallosal striae. By 2 weeks posttransection, the extent of neuronal loss was 50% of the total neurons and 70% of the cholinergic neurons in the MS and 30% of the total neurons and 40% of the cholinergic neurons in the VDB. We hypothesized that (i) the death was due to the loss of a hippocampus-derived neuronotrophic factor, and (ii) exogenous nerve growth factor (NGF) might provide trophic support to the MS/VDB cholinergic neurons, in light of recent reports that the septal diagonal band cholinergic neurons are responsive to NGF and that NGF is present and produced in the hippocampus. In the present study, we attempted to prevent the transection-induced neuronal death by continuous infusion of exogenous 7S NGF (1 .mu.g/wk) through an intraventricular cannula device. We report here that NGF treatment significantly reduces both the total neuronal and cholinergic neuronal death found 2 weeks after fimbria fornix transection; there was a sparing of 50% of the neurons in the MS and essentially 100% of those in the VDB that otherwise would have died. We conclude that NGF also has a protective effect on noncholinergic neurons since calculations indicate that 80% of the NGF-affected neurons are noncholinergic.