Garraway Sandra M, Anderson Aileen J, Mendell Lorne M
Department of Neurobiology and Behavior, 550 Life Sciences Bldg., State University of New York, Stony Brook, New York 11794-5230, USA.
J Neurophysiol. 2005 Sep;94(3):1798-804. doi: 10.1152/jn.00179.2005. Epub 2005 May 18.
We previously reported that brain-derived neurotrophic factor (BDNF), a pronociceptive neurotransmitter, induces synaptic facilitation of excitatory postsynaptic current (EPSC) in lamina II neurons of neonatal rats up to P14 in a N-methyl-d-aspartate (NMDA) receptor-dependent manner. Here we used the patch-clamp technique to study synaptic and NMDA-evoked responses in transverse spinal slices in the lumbar enlargement as well as the ability of BDNF to modify these responses from 1 day to 6 wk after neonatal contusion. In older uninjured animals (>P14), BDNF continued to evoke synaptic facilitation although superfusion of NMDA (in TTX) induced inward current of significantly smaller amplitude than that observed in younger rats. After contusion injury, BDNF was unable to facilitate dorsal root-evoked EPSCs in lamina II neurons despite the finding that NMDA-evoked currents were only slightly smaller than those observed in age-matched uninjured animals. These findings suggest that although BDNF-induced facilitation of the AMPA/kainate receptor-mediated response to dorsal root stimulation is maintained in the mature dorsal horn from intact rats, BDNF may no longer elicit these pronociceptive actions after neonatal contusion injury. The lack of change in NMDA-evoked currents in contused cords suggests that diminished NMDA receptor function is not the major cause of the decline in BDNF action after contusion. It seems more likely that diminished trkB expression and enhanced expression of truncated trkB receptors in the contused cord play a significant role in determining the reduced effect of BDNF under these conditions.
我们先前报道过，脑源性神经营养因子（BDNF）作为一种伤害感受性神经递质，以N-甲基-D-天冬氨酸（NMDA）受体依赖的方式，在出生后14天内的新生大鼠Ⅱ层神经元中诱导兴奋性突触后电流（EPSC）的突触易化。在此，我们采用膜片钳技术，研究腰膨大横断脊髓切片中的突触反应和NMDA诱发反应，以及脑源性神经营养因子在新生大鼠挫伤后1天至6周改变这些反应的能力。在年龄较大的未受伤动物（>出生后14天）中，脑源性神经营养因子继续诱发突触易化，尽管在TTX存在下灌流NMDA所诱发的内向电流幅度明显小于年幼大鼠。挫伤后，尽管发现NMDA诱发的电流仅略小于年龄匹配的未受伤动物，但脑源性神经营养因子无法促进Ⅱ层神经元中背根诱发的EPSC。这些发现表明，尽管在完整大鼠的成熟背角中，脑源性神经营养因子诱导的对背根刺激的AMPA/海人藻酸受体介导反应的易化得以维持，但新生大鼠挫伤后，脑源性神经营养因子可能不再引发这些伤害感受性作用。挫伤脊髓中NMDA诱发电流没有变化，这表明NMDA受体功能减弱不是挫伤后脑源性神经营养因子作用下降的主要原因。在这些条件下，似乎更有可能的是，挫伤脊髓中trkB表达减少和截短的trkB受体表达增加，在决定脑源性神经营养因子作用减弱方面发挥了重要作用。
