Activity-dependent activation of TrkB neurotrophin receptors in the adult CNS.

Activity-dependent activation of TrkB neurotrophin receptors in the adult CNS.
复制标题

成人中枢神经系统中 TrkB 神经营养蛋白受体的活性依赖性激活。

DOI:
10.1101/lm.6.3.216
复制
发表时间:
1999
期刊:
影响因子:
2
通讯作者:
F. Miller
F. Miller
中科院分区:
医学4区
文献类型:
--
作者:
R. Aloyz;J. P. Fawcett;David L. Kaplan;R. A. Murphy;F. Miller

文献摘要

参考文献

被引文献

相似文献

在本文中,我们已经调查的假设,神经活动导致快速激活的TrkB神经营养因子受体在成年哺乳动物中枢神经系统。这些研究表明,红藻氨酸诱导的癫痫发作导致皮质中TrkB受体的快速和短暂激活。亚细胞分级分离表明,这些激活的Trk受体优先富集在突触体膜部分,也含有突触后谷氨酸受体。快速激活的突触TrkB受体可以复制在孤立的皮质突触体与KCl,可能是由于去极化诱导的BDNF释放。重要的是,在合成和顺向转运BDNF的脑干去甲肾上腺素能神经元的药理学激活后也观察到TrkB激活;用育亨宾处理导致皮质TrkB受体在30分钟内活化。用哌唑嗪对突触后α 1-肾上腺素能受体的药理学阻断仅部分抑制该作用,表明TrkB激活部分是由于对突触后皮质神经元的直接作用。总之,这些数据支持这样的假设,即活动导致BDNF从突触前末梢释放,导致突触后TrkB受体的快速激活。这种活性依赖性的TrkB激活可以在发育和成熟的神经系统的形态生长和重塑中发挥重要作用。
In this paper we have investigated the hypothesis that neural activity causes rapid activation of TrkB neurotrophin receptors in the adult mammalian CNS. These studies demonstrate that kainic acid-induced seizures led to a rapid and transient activation of TrkB receptors in the cortex. Subcellular fractionation demonstrated that these activated Trk receptors were preferentially enriched in the synaptosomal membrane fraction that also contained postsynaptic glutamate receptors. The fast activation of synaptic TrkB receptors could be duplicated in isolated cortical synaptosomes with KCl, presumably as a consequence of depolarization-induced BDNF release. Importantly, TrkB activation was also observed following pharmacological activation of brain-stem noradrenergic neurons, which synthesize and anterogradely transport BDNF; treatment with yohimbine led to activation of cortical TrkB receptors within 30 min. Pharmacological blockade of the postsynaptic alpha1-adrenergic receptors with prazosin only partially inhibited this effect, suggesting that the TrkB activation was partially due to a direct effect on postsynaptic cortical neurons. Together, these data support the hypothesis that activity causes release of BDNF from presynaptic terminals, resulting in a rapid activation of postsynaptic TrkB receptors. This activity-dependent TrkB activation could play a major role in morphological growth and remodelling in both the developing and mature nervous systems.
DOI: 10.1016/s0021-9258(18)43787-8
发表时间: 1994-12
期刊: The Journal of biological chemistry
影响因子: --
作者:
Peter S. McPherson;Kohji Takei;Sandra L. Schmid;P. D. Camilli
通讯作者: Peter S. McPherson;Kohji Takei;Sandra L. Schmid;P. D. Camilli
DOI: 10.1073/pnas.95.17.10235
发表时间: 1998-08-18
影响因子: 11.1
作者:
Levine, ES;Crozier, RA;Plummer, MR
通讯作者: Plummer, MR
DOI: 10.1073/pnas.94.15.8191
发表时间: 1997-07-22
影响因子: 11.1
作者:
Suen, PC;Wu, K;Black, IB
通讯作者: Black, IB
DOI: 10.1073/pnas.92.17.8074
发表时间: 1995-08-15
影响因子: 11.1
作者:
LEVINE, ES;DREYFUS, CF;PLUMMER, MR
通讯作者: PLUMMER, MR
DOI: 10.1126/science.7907431
发表时间: 1994-03-18
期刊: SCIENCE
影响因子: 56.9
作者:
GHOSH, A;CARNAHAN, J;GREENBERG, ME
通讯作者: GREENBERG, ME