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神经营养因子在突触发育和可塑性中的作用。

Role of neurotrophins in synapse development and plasticity.

作者信息

Lu B, Figurov A

机构信息

Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892-4480, USA.

出版信息

Rev Neurosci. 1997 Jan-Mar;8(1):1-12. doi: 10.1515/revneuro.1997.8.1.1.

Abstract

Neurotrophic factors are traditionally viewed as secretory proteins that regulate long-term survival and differentiation of neurons. The role of neurotrophic factors in the structural integrity of the nervous system makes them attractive candidates as therapeutic agents for neurodegenerative diseases. However, the fact that expression of many neurotrophic factors in the central nervous system is rapidly enhanced by neuronal activity suggests a new role for these factors in activity-dependent processes, such as synaptic development and plasticity. A series of recent studies has provided strong evidence for this novel function of neurotrophic factors. The neurotrophin family of proteins has been shown to acutely potentiate synaptic transmission at the neuromuscular junction and in the brain. These factors are also involved in the maturation of the neuromuscular synapses and in the development of synapses in the visual system. Gene targeting and physiological experiments demonstrate that brain-derived neurotrophic factor (BDNF) plays an important role in long-term potentiation (LTP), a cellular model for learning and memory. These findings have brought together two hotly pursued areas of neuroscience, namely, the function of neurotrophic factors and the mechanisms for synaptic plasticity. Continuous studies in this new field will help understand how synapses develop and function in the brain, and may have significant implications in treating learning disorders in both children and adults.

摘要

传统上,神经营养因子被视为调节神经元长期存活和分化的分泌蛋白。神经营养因子在神经系统结构完整性方面的作用,使其成为神经退行性疾病治疗药物的有吸引力的候选者。然而,许多神经营养因子在中枢神经系统中的表达会因神经元活动而迅速增强,这一事实表明这些因子在诸如突触发育和可塑性等活动依赖性过程中具有新的作用。最近的一系列研究为神经营养因子的这一新功能提供了有力证据。已表明神经营养蛋白家族的蛋白质能在神经肌肉接头和大脑中急性增强突触传递。这些因子还参与神经肌肉突触的成熟以及视觉系统中突触的发育。基因靶向和生理学实验表明,脑源性神经营养因子(BDNF)在长时程增强(LTP)中起重要作用,LTP是学习和记忆的细胞模型。这些发现将神经科学中两个备受关注的领域结合在一起,即神经营养因子的功能和突触可塑性的机制。在这个新领域的持续研究将有助于理解大脑中突触如何发育和发挥功能,并且可能对治疗儿童和成人的学习障碍具有重要意义。

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