In Vivo Imaging of Dorsal Root Regeneration: Rapid Immobilization and Presynaptic Differentiation at the CNS/PNS Border

被引:72
作者
Di Maio, Alessandro [2 ]
Skuba, Andrew [1 ,2 ]
Himes, B. Timothy [2 ,3 ]
Bhagat, Srishiti L. [2 ]
Hyun, Jung Keun [2 ,4 ]
Tessler, Alan [2 ,3 ]
Bishop, Derron [5 ]
Son, Young-Jin [1 ,2 ,4 ]
机构
[1] Temple Univ, Sch Med, Shriners Hosp, Pediat Res Ctr,Dept Anat & Cell Biol, Philadelphia, PA 19140 USA
[2] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA
[3] Dept Vet Affairs Hosp, Dept Neurol, Philadelphia, PA 19104 USA
[4] Dankook Univ, WCU Nanobiomed Sci Res Ctr, Cheonan 330714, South Korea
[5] Indiana Univ Sch Med, Dept Med Educ, Muncie, IN 47306 USA
关键词
OLIGODENDROCYTE PRECURSOR CELLS; SPINAL-CORD; SENSORY AXONS; ENTRY ZONE; NEURITE OUTGROWTH; GROWTH CONE; FUNCTIONAL REGENERATION; NOGO; PROTEOGLYCANS; INHIBITION;
D O I
10.1523/JNEUROSCI.4638-10.2011
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Dorsal root (DR) axons regenerate in the PNS but turn around or stop at the dorsal root entry zone (DREZ), the entrance into the CNS. Earlier studies that relied on conventional tracing techniques or postmortem analyses attributed the regeneration failure to growth inhibitors and lack of intrinsic growth potential. Here, we report the first in vivo imaging study of DR regeneration. Fluorescently labeled, large-diameter DR axons in thy1-YFPH mice elongated through a DR crush site, but not a transection site, and grew along the root at >1.5 mm/d with little variability. Surprisingly, they rarely turned around at the DREZ upon encountering astrocytes, but penetrated deeper into the CNS territory, where they rapidly stalled and then remained completely immobile or stable, even after conditioning lesions that enhanced growth along the root. Stalled axon tips and adjacent shafts were intensely immunolabeled with synapse markers. Ultrastructural analysis targeted to the DREZ enriched with recently arrived axons additionally revealed abundant axonal profiles exhibiting presynaptic features such as synaptic vesicles aggregated at active zones, but not postsynaptic features. These data suggest that axons are neither repelled nor continuously inhibited at the DREZ by growth-inhibitory molecules but are rapidly stabilized as they invade the CNS territory of the DREZ, forming presynaptic terminal endings on non-neuronal cells. Our work introduces a new experimental paradigm to the investigation of DR regeneration and may help to induce significant regeneration after spinal root injuries.
引用
收藏
页码:4569 / 4582
页数:14
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