Giehl K M, Schütte A, Mestres P, Yan Q
Anatomisches Institut, Universität des Saarlandes, D-66421 Homburg/Saar, Germany.
J Neurosci. 1998 Sep 15;18(18):7351-60. doi: 10.1523/JNEUROSCI.18-18-07351.1998.
Autocrine trophic functions of brain-derived neurotrophic factor (BDNF) have been proposed for many central neurons because this neurotrophin displays striking colocalization with its receptor trkB within the CNS. In the cortex, the distribution patterns of BDNF and trkB expression are almost identical. Corticospinal neurons (CSNs) are a major cortical long-distance projecting system. They are localized in layer V of the somatosensory cortex, and their axons project into the spinal cord where they contribute to the innervation of spinal motoneurons. We have shown recently that adult CSNs express trkB mRNA and are rescued from axotomy-induced death by BDNF treatment. Half of the axotomized CSNs survived without BDNF infusions. These findings raise the possibility that endogenous cortical BDNF is involved in the trophic support of this neuronal population. To test the hypothesis that endogenous cortical BDNF promotes survival of adult CSNs, we infused the BDNF-neutralizing affinity-purified antibody RAB to axotomized and unlesioned CSNs for 7 d. This treatment resulted in increased death of axotomized CSNs. Survival of unlesioned CSNs was not affected by RAB treatment. In situ hybridizations for BDNF and trkB mRNA revealed that virtually all CSNs express trkB, whereas only half of them express BDNF. Thus, autocrine/paracrine mechanisms are likely to contribute to the endogenous BDNF protection of axotomized CSNs. We have demonstrated previously that, in addition to BDNF, glial cell line-derived neurotrophic factor (GDNF) and neurotrophin 3 (NT-3) also rescue CSNs from axotomy-induced death. We now show that the rescuing by GDNF requires the presence of endogenous cortical BDNF, implicating a central role of this neurotrophin in the trophic support of axotomized CSNs and a trophic cross-talk between BDNF and GDNF regarding the maintenance of lesioned CSNs. In contrast, NT-3 promotes survival of axotomized CSNs even when endogenous cortical BDNF is neutralized by RAB, indicating a potential of compensatory mechanisms for the trophic support of CSNs.
脑源性神经营养因子（BDNF）的自分泌营养功能已被认为存在于许多中枢神经元中，因为这种神经营养因子与其受体trkB在中枢神经系统（CNS）内表现出显著的共定位。在皮质中，BDNF和trkB表达的分布模式几乎相同。皮质脊髓神经元（CSNs）是主要的皮质长距离投射系统。它们位于体感皮质的第V层，其轴突投射到脊髓，在那里它们参与脊髓运动神经元的神经支配。我们最近发现，成年CSNs表达trkB mRNA，并且通过BDNF治疗可使其从轴突切断诱导的死亡中获救。一半的轴突切断的CSNs在没有BDNF注入的情况下存活。这些发现增加了内源性皮质BDNF参与该神经元群体营养支持的可能性。为了检验内源性皮质BDNF促进成年CSNs存活的假设，我们将BDNF中和亲和纯化抗体RAB注入轴突切断和未损伤的CSNs中7天。这种治疗导致轴突切断的CSNs死亡增加。未损伤的CSNs的存活不受RAB治疗的影响。BDNF和trkB mRNA的原位杂交显示，几乎所有的CSNs都表达trkB，而只有一半表达BDNF。因此，自分泌/旁分泌机制可能有助于内源性BDNF对轴突切断的CSNs的保护。我们之前已经证明，除了BDNF，胶质细胞系源性神经营养因子（GDNF）和神经营养因子3（NT-3）也能使CSNs从轴突切断诱导的死亡中获救。我们现在表明，GDNF的拯救作用需要内源性皮质BDNF的存在，这表明这种神经营养因子在轴突切断的CSNs的营养支持中起核心作用，并且在BDNF和GDNF之间存在关于受损CSNs维持的营养相互作用。相比之下，即使内源性皮质BDNF被RAB中和，NT-3仍能促进轴突切断的CSNs的存活，这表明存在CSNs营养支持的潜在补偿机制。
