O'Neill Kate M, Kwon Munjin, Donohue Katherine E, Firestein Bonnie L
Department of Cell Biology & Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ, 08854, USA.
Graduate Program in Biomedical Engineering Rutgers University, Piscataway, NJ, USA.
Cell Mol Life Sci. 2017 Dec;74(23):4369-4385. doi: 10.1007/s00018-017-2589-7. Epub 2017 Jul 11.
Proper communication among neurons depends on an appropriately formed dendritic arbor, and thus, aberrant changes to the arbor are implicated in many pathologies, ranging from cognitive disorders to neurodegenerative diseases. Due to the importance of dendritic shape to neuronal network function, the morphology of dendrites is tightly controlled and is influenced by both intrinsic and extrinsic factors. In this work, we examine how brain-derived neurotrophic factor (BDNF), one of the most well-studied extrinsic regulators of dendritic branching, affects the arbor when it is applied locally via microbeads to cultures of hippocampal neurons. We found that local application of BDNF increases both proximal and distal branching in a time-dependent manner and that local BDNF application attenuates pruning of dendrites that occurs with neuronal maturation. Additionally, we examined whether cytosolic PSD-95 interactor (cypin), an intrinsic regulator of dendritic branching, plays a role in these changes and found strong evidence for the involvement of cypin in BDNF-promoted increases in dendrites after 24 but not 48 h of application. This current study extends our previous work in which we found that bath application of BDNF for 72 h, but not shorter times, increases proximal dendrite branching and that this increase occurs through transcriptional regulation of cypin. Moreover, this current work illustrates how dendritic branching is regulated differently by the same growth factor depending on its spatial localization, suggesting a novel pathway for modulation of dendritic branching locally.
神经元之间的正常通讯依赖于适当形成的树突分支，因此，树突分支的异常变化与许多病理状况有关，范围从认知障碍到神经退行性疾病。由于树突形状对神经网络功能的重要性，树突的形态受到严格控制，并受内在和外在因素的影响。在这项研究中，我们研究了脑源性神经营养因子（BDNF），一种研究最为充分的树突分支外在调节因子，当通过微珠局部应用于海马神经元培养物时，是如何影响树突分支的。我们发现，局部应用BDNF会以时间依赖的方式增加近端和远端分支，并且局部应用BDNF会减弱神经元成熟时发生的树突修剪。此外，我们研究了树突分支的内在调节因子胞质PSD-95相互作用蛋白（cypin）是否在这些变化中起作用，并发现有强有力的证据表明，在应用BDNF 24小时而非48小时后，cypin参与了BDNF促进的树突增加。这项研究扩展了我们之前的工作，在之前的工作中我们发现，BDNF浸泡处理72小时（而非更短时间）会增加近端树突分支，并且这种增加是通过cypin的转录调控实现的。此外，这项研究还说明了同一生长因子根据其空间定位对树突分支的调控方式不同，这提示了一种局部调节树突分支的新途径。
