Quantitative analysis of multivesicular bodies (MVBs) in the hypoglossal nerve: evidence that neurotrophic factors do not use MVBs for retrograde axonal transport.

Quantitative analysis of multivesicular bodies (MVBs) in the hypoglossal nerve: evidence that neurotrophic factors do not use MVBs for retrograde axonal transport.
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DOI:
10.1002/cne.22047
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发表时间:
2009-06-20
期刊:
The Journal of comparative neurology
影响因子:
--
通讯作者:
von Bartheld CS
von Bartheld CS
中科院分区:
其他
文献类型:
--
作者:
Altick AL;Baryshnikova LM;Vu TQ;von Bartheld CS

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多泡小体(MVB)是由包裹在外界膜内的多个内部小泡定义的。MVB在神经元胞体和树突中已经被定量,但它们在轴突中的频率和意义仍有争议。尽管缺乏确凿的证据,但人们普遍认为MVB是轴突中携带神经营养因子的主要细胞器。轴突微血管在生理和病理条件下的可靠信息对于真实评估它们在神经元中的功能作用是必要的。我们提供了在各种实验条件下正常出生的大鼠舌下神经中微血管的定量超微结构分析。轴突中MVB的发生率约为神经元胞体或树突中MVB的50倍。根据MVB的大小、电子密度和内部小泡的大小,在轴突中可以区分出五种不同的MVB类型。虽然靶操作没有显著改变轴突中的MVB,但营养不良条件,如延迟固定,显著增加了轴突MVB的数量。通过定量超微结构放射自显影和量子点标记的BDNF分析证实,注射到舌内的放射性标记的脑和胶质细胞源性神经营养因子(BDNF和GDNF)在MVB的逆行轴突运输过程中没有积聚。我们的结论是,对于轴突运输,神经营养因子利用在透射电子显微镜分辨率下可能不明显的小囊泡或内小体,而不是微血管。以前关于轴突MVB的报道可能部分是基于营养不良条件下在轴突中人工产生这样的细胞器。
Multivesicular bodies (MVBs) are defined by multiple internal vesicles enclosed within an outer, limiting membrane. MVBs have previously been quantified in neuronal cell bodies and in dendrites, but their frequencies and significance in axons are controversial. Despite lack of conclusive evidence, it is widely believed that MVBs are the primary organelle that carries neurotrophic factors in axons. Reliable information about axonal MVBs under physiological and pathological conditions is needed for a realistic assessment of their functional roles in neurons. We provide a quantitative ultrastructural analysis of MVBs in the normal postnatal rat hypoglossal nerve and under a variety of experimental conditions. MVBs were about 50 times less frequent in axons than in neuronal cell bodies or dendrites. Five distinct types of MVBs were distinguished in axons, based on MVB size, electron density and size of internal vesicles. While target manipulations did not significantly change MVBs in axons, dystrophic conditions such as delayed fixation substantially increased the number of axonal MVBs. Radiolabeled brain- and glial-cell derived neurotrophic factors (BDNF and GDNF) injected into the tongue did not accumulate during retrograde axonal transport in MVBs, as determined by quantitative ultrastructural autoradiography, and confirmed by analysis of quantum dot-labeled BDNF. We conclude that for axonal transport, neurotrophic factors utilize small vesicles or endosomes that can be inconspicuous at transmission electron microscopic resolution, rather than MVBs. Previous reports of axonal MVBs may be based, in part, on artificial generation of such organelles in axons due to dystrophic conditions.
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