Howard Hughes Medical Institute, Department of Physiology, Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94158, USA.
Genes Dev. 2018 Mar 1;32(5-6):402-414. doi: 10.1101/gad.308270.117. Epub 2018 Mar 21.
Dendrites possess distinct structural and functional properties that enable neurons to receive information from the environment as well as other neurons. Despite their key role in neuronal function, current understanding of the ability of neurons to regenerate dendrites is lacking. This study characterizes the structural and functional capacity for dendrite regeneration in vivo in adult animals and examines the effect of neuronal maturation on dendrite regeneration. We focused on the class IV dendritic arborization (c4da) neuron of the sensory system, which has a dendritic arbor that undergoes dramatic remodeling during the first 3 d of adult life and then maintains a relatively stable morphology thereafter. Using a laser severing paradigm, we monitored regeneration after acute and spatially restricted injury. We found that the capacity for regeneration was present in adult neurons but diminished as the animal aged. Regenerated dendrites recovered receptive function. Furthermore, we found that the regenerated dendrites show preferential alignment with the extracellular matrix (ECM). Finally, inhibition of ECM degradation by inhibition of matrix metalloproteinase 2 (Mmp2) to preserve the extracellular environment characteristics of young adults led to increased dendrite regeneration. These results demonstrate that dendrites retain regenerative potential throughout adulthood and that regenerative capacity decreases with aging.
树突具有独特的结构和功能特性，使神经元能够接收环境以及其他神经元的信息。尽管它们在神经元功能中起着关键作用，但目前对神经元再生树突的能力的理解还很缺乏。本研究在体内对成年动物的树突再生的结构和功能能力进行了描述，并研究了神经元成熟对树突再生的影响。我们集中研究了感觉系统中的 IV 类树突状分支（c4da）神经元，其树突在成年后的头 3 天经历剧烈重塑，此后保持相对稳定的形态。我们使用激光切断范式，监测急性和空间限制损伤后的再生情况。我们发现再生能力存在于成年神经元中，但随着动物年龄的增长而减弱。再生的树突恢复了接收功能。此外，我们发现再生的树突表现出与细胞外基质（ECM）的优先对齐。最后，通过抑制基质金属蛋白酶 2（Mmp2）抑制 ECM 降解以保留年轻成年的细胞外环境特征，导致树突再生增加。这些结果表明，树突在整个成年期都保持着再生潜力，并且再生能力随着年龄的增长而下降。
