Lim Kuei-Cheng, Lim Seung T, Federoff Howard J
Interdepartmental Program in Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Neurobiol Aging. 2003 Dec;24(8):1135-45. doi: 10.1016/j.neurobiolaging.2003.09.003.
Neurotrophins and synaptic activity work in conjunction during the process of synaptic plasticity. Both are required to stabilize new synaptic structures and the loss of either can lead to cognitive impairments, as new information cannot be stored efficiently or later recalled. Neurotrophins are becoming recognized as mediators of activity-dependent plasticity. The synthesis and release of neurotrophins follow neurosecretory pathways. They are synthesized as immature, pro-neurotrophin molecules, processed, and then mature forms are secreted. These then activate distinct signal tranduction pathways that modify the synapse. High frequency stimulation is known to induce long-term potentiation (LTP) and synaptic enhancement, however, the stability of these changes requires a bi-directional communication between the pre- and post-synaptic terminals and neurotrophins can function in such a capacity. The NGFXAT somatic mosaic murine model demonstrated how neurotrophin and active learning induces a robust synaptic reorganization. Synaptic dysfunction decreases efficient neurotransmission or neurotrophin production and then precedes overt neurodegeneration. The study of synaptic dysfunction and neurotrophin actions with respect to activity will lead to future therapeutic interventions of age-related dementias.
神经营养因子和突触活动在突触可塑性过程中协同发挥作用。两者对于稳定新的突触结构都是必需的，并且任何一方的缺失都可能导致认知障碍，因为新信息无法有效存储或随后被回忆起来。神经营养因子正被视为活动依赖性可塑性的介质。神经营养因子的合成和释放遵循神经分泌途径。它们以未成熟的前神经营养因子分子形式合成，经过加工，然后分泌成熟形式。这些成熟形式随后激活不同的信号转导途径来修饰突触。已知高频刺激可诱导长时程增强（LTP）和突触增强，然而，这些变化的稳定性需要突触前和突触后终末之间的双向通信，而神经营养因子可以发挥这样的作用。NGFXAT体细胞镶嵌小鼠模型展示了神经营养因子和主动学习如何诱导强大的突触重组。突触功能障碍会降低神经传递效率或神经营养因子的产生，然后在明显的神经退行性变之前出现。关于活动对突触功能障碍和神经营养因子作用的研究将为未来与年龄相关的痴呆症治疗干预提供方向。
