Influence of brain-derived neurotrophic factor on pathfinding of dentate granule cell axons, the hippocampal mossy fibers.
Influence of brain-derived neurotrophic factor on pathfinding of dentate granule cell axons, the hippocampal mossy fibers.
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DOI：
10.1186/1756-6606-2-2
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发表时间：
2009-01-31
期刊：
影响因子：
3.6
通讯作者：
Yamada, Maki K.
中科院分区：
文献类型：
--
作者：
Tamura, Makoto;Tamura, Naohiro;Ikeda, Takamitsu;Koyama, Ryuta;Ikegaya, Yuji;Matsuki, Norio;Yamada, Maki K.
苔藓纤维，齿状颗粒细胞轴突，在动物的一生中产生。苔藓纤维路径和突触主要限于CA 3区域内的透明层。脑源性神经营养因子（BDNF）是一种激活Trk神经营养因子受体的神经营养因子家族蛋白，其以活性依赖性方式在透明层中高度表达。此外，一个Trk神经营养因子受体抑制剂，K252 a，培养海马切片诱导苔藓纤维异常延伸到异位区域。BDNF在颗粒细胞中的过表达改善了由次最大剂量的K252 a引起的苔藓纤维通路异常。当BDNF在CA 3锥体细胞中表达时，观察到类似的救援，最明显的是在表达位点远端的苔藓纤维中。这些发现是第一个澄清的作用，BDNF在苔藓纤维寻路，而不是作为一个引诱剂的线索，但作为一个调节器，可能在旁分泌的方式行事。BDNF的这种作用可能是作为一个信号，使新的纤维成束并进一步延伸，与远离活性BDNF表达突触的神经元形成突触。这种机制将确保新生颗粒细胞轴突产生新的独立齿状回-CA 3回路。
Mossy fibers, the dentate granule cell axons, are generated throughout an animal's lifetime. Mossy fiber paths and synapses are primarily restricted to the stratum lucidum within the CA3 region. Brain-derived neurotrophic factor (BDNF), a neurotrophin family protein that activates Trk neurotrophin receptors, is highly expressed in the stratum lucidum in an activity-dependent manner. The addition of a Trk neurotrophin receptor inhibitor, K252a, to cultured hippocampal slices induced aberrant extension of mossy fibers into ectopic regions. BDNF overexpression in granule cells ameliorated the mossy fiber pathway abnormalities caused by a submaximal dose of K252a. A similar rescue was observed when BDNF was expressed in CA3 pyramidal cells, most notably in mossy fibers distal to the expression site. These findings are the first to clarify the role of BDNF in mossy fiber pathfinding, not as an attractant cue but as a regulator, possibly acting in a paracrine manner. This effect of BDNF may be as a signal for new fibers to fasciculate and extend further to form synapses with neurons that are far from active BDNF-expressing synapses. This mechanism would ensure the emergence of new independent dentate gyrus-CA3 circuits by the axons of new-born granule cells.
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影响因子：
46.9
作者：
Nagai, T;Ibata, K;Miyawaki, A
通讯作者：
Miyawaki, A
影响因子：
3.5
作者：
Bekirov, Iddil H.;Nagy, Vanja;Benson, Deanna L.
通讯作者：
Benson, Deanna L.
影响因子：
5.3
作者：
Danzer, SC;McNamara, JO
通讯作者：
McNamara, JO
影响因子：
64.8
作者：
Li, Y;Jia, YC;Yuan, XB
通讯作者：
Yuan, XB
DOI：
10.1073/pnas.0806658105
发表时间：
2008-09-16
影响因子：
11.1
作者：
Faulkner, Regina L.;Jang, Mi-Hyeon;Cheng, Hwai-Jong
通讯作者：
Cheng, Hwai-Jong