中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (3): 363-367.doi: 10.4103/1673-5374.179031

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

脑源性神经营养因子如何重塑大脑?

  

  • 收稿日期:2016-01-05 出版日期:2016-03-15 发布日期:2016-03-15
  • 基金资助:

    HB和EK由美国国立卫生研究院NS034007和NS047384资助支持。MVC由美国国立卫生研究院NS21072和HD23315资助支持。AB由印度政府生物技术部门资金支助以及印度和尚塔━瓦德瓦尼基金会资助。

Deconstructing brain-derived neurotrophic factor actions in adult brain circuits to bridge an existing informational gap in neuro-cell biology

Heather Bowling 1, Aditi Bhattacharya 2, Eric Klann 1, Moses V. Chao 3   

  1. 1 Center for Neural Science, New York University, New York, NY, USA
    2 Center for Brain Development and Repair, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India
    3 Departments of Cell Biology, Physiology, and Neuroscience and Psychiatry, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY, USA
  • Received:2016-01-05 Online:2016-03-15 Published:2016-03-15
  • Contact: Heather Bowling, Ph.D., or Aditi Bhattacharya, Ph.D., aditi@instem.res.in or hlb248@nyu.edu
  • Supported by:

    HB and EK were supported by NIH grants NS034007 and NS047384. MVC was supported by NIH grants NS21072, and HD23315. AB was supported by funds from the Department of Biotechnology, Government of India and the Shanta Wadhwani Foundation.

摘要:

脑源性神经营养因子在神经发育、突触可塑性、学习和记忆以及预防神经退行性病中发挥着重要作用。尽管对下游信号通路和改变细胞过程的研究已经进行了几十年,但脑源性神经营养因子信号是如何重塑电路的机制仍不清楚。在培养的神经元中进行的大部分研究已深入到脑源性神经营养因子分子行为,而大多数脑源性神经营养因子和突触可塑性,学习和记忆研究需要在急性脑切片或体内进行,因此得出的数据出现了断层。为了帮助弥合目前所知的成年脑回路中脑源性神经营养因子机制的这种差距,我们实验室测得了急性成年海马切片在进行1小时脑源性神经营养因子治疗后的蛋白质组变化并报告了有关突触释放和分泌蛋白的重要变化。另外,他们也检测到了与血液相关的蛋白质,这表明脑血流事件在突触可塑性中的潜在作用。文章将这些发现整合到现有文献当中并讨论了脑源性神经营养因子如何重塑大脑的理解。该研究提供的新数据对理解脑源性神经营养因子作用机制十分重要,形成了该领域中新的研究问题,最后文章回答小配体,如脑源性神经营养因子是如何深刻地改变脑回路以及负责大规模学习和记忆变化的问题。

Abstract:

Brain-derived neurotrophic factor (BDNF) plays an important role in neurodevelopment, synaptic plasticity,learning and memory, and in preventing neurodegeneration. Despite decades of investigations into downstream signaling cascades and changes in cellular processes, the mechanisms of how BDNF reshapes circuits in vivo remain unclear. This informational gap partly arises from the fact that the bulk of studies into the molecular actions of BDNF have been performed in dissociated neuronal cultures, while the majority of studies on synaptic plasticity, learning and memory were performed in acute brain slices or in vivo. A recent study by Bowling-Bhattacharya et al., measured the proteomic changes in acute adult hippocampal slices following treatment and reported changes in proteins of neuronal and non-neuronal origin that may in concert modulate synaptic release and secretion in the slice. In this paper, we place these findings into the context of existing literature and discuss how they impact our understanding of how BDNF can reshape the brain

Key words: BONLAC, BDNF, adult slice proteomics, neuroproteomics, SILAC, BONCAT, hippocampus, protein synthesis