Pazyra-Murphy Maria F, Segal Rosalind A
Department of Pediatric Oncology, Dana-Farber Cancer Institute, USA.
J Vis Exp. 2008 Oct 17(20):951. doi: 10.3791/951.
Neurons extend axonal processes that are far removed from the cell body to innervate target tissues, where target-derived growth factors are required for neuronal survival and function. Neurotrophins are specifically required to maintain the survival and differentiation of innervating sensory neurons but the question of how these target-derived neurotrophins communicate to the cell body of innervating neurons has been an area of active research for over 30 years. The most commonly accepted model of how neurotrophin signals reach the cell body proposes that signaling endosomes carry this signal retrogradely along the axon. In order to study retrograde transport, a culture system was originally devised by Robert Campenot, in which cell bodies are isolated from their axons. The technique of preparing these compartmented chambers for culturing sensory neurons recapitulates the selective stimulation of neuron terminals that occurs in vivo following release of target-derived neurotrophins. Retrograde signaling events that require long-range microtubule dependent retrograde transport have important implications for the treatment of neurodegenerative disorders.
神经元伸出远离细胞体的轴突过程以支配靶组织,而神经元的存活和功能需要靶源性生长因子。神经营养因子是维持支配性感觉神经元存活和分化所特需的,但这些靶源性神经营养因子如何与支配性神经元的细胞体进行通信的问题,30多年来一直是活跃的研究领域。关于神经营养因子信号如何到达细胞体,最被广泛接受的模型认为,信号内体沿着轴突逆向携带该信号。为了研究逆向运输,罗伯特·坎佩诺特最初设计了一种培养系统,其中细胞体与其轴突分离。制备这些用于培养感觉神经元的分隔小室的技术,概括了体内靶源性神经营养因子释放后发生的神经元终末的选择性刺激。需要长距离微管依赖性逆向运输的逆向信号事件,对神经退行性疾病的治疗具有重要意义。