Fenrich Keith K, Skelton Nicole, MacDermid Victoria E, Meehan Claire F, Armstrong Stacey, Neuber-Hess Monica S, Rose P Ken
CIHR Group in Sensory-Motor Systems, Department of Physiology, Center for Neuroscience, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
J Comp Neurol. 2007 Jun 20;502(6):1079-97. doi: 10.1002/cne.21362.
Following proximal axotomy, several types of neurons sprout de novo axons from distal dendrites. These processes may represent a means of forming new circuits following spinal cord injury. However, it is not know whether mammalian spinal interneurons, axotomized as a result of a spinal cord injury, develop de novo axons. Our goal was to determine whether spinal commissural interneurons (CINs), axotomized by 3-4-mm midsagittal transection at C3, form de novo axons from distal dendrites. All experiments were performed on adult cats. CINs in C3 were stained with extracellular injections of Neurobiotin at 4-5 weeks post injury. The somata of axotomized CINs were identified by the presence of immunoreactivity for the axonal growth-associated protein-43 (GAP-43). Nearly half of the CINs had de novo axons that emerged from distal dendrites. These axons lacked immunoreactivity for the dendritic protein, microtubule-associated protein2a/b (MAP2a/b); some had GAP-43-immunoreactive terminals; and nearly all had morphological features typical of axons. Dendrites of other CINs did not give rise to de novo axons. These CINs did, however, each have a long axon-like process (L-ALP) that projected directly from the soma or a very proximal dendrite. L-ALPs were devoid of MAP2a/b immunoreactivity. Some of these L-ALPs projected through the lesion and formed bouton-like swellings. These results suggest that proximally axotomized spinal interneurons have the potential to form new connections via de novo axons that emerge from distal dendrites. Others may be capable of regeneration of their original axon.
在近端轴突切断后,几种类型的神经元会从远端树突长出新生轴突。这些过程可能代表了脊髓损伤后形成新回路的一种方式。然而,尚不清楚因脊髓损伤而被轴突切断的哺乳动物脊髓中间神经元是否会发育出新生轴突。我们的目标是确定在C3水平进行3 - 4毫米矢状面中段横切而被轴突切断的脊髓连合中间神经元(CINs)是否会从远端树突形成新生轴突。所有实验均在成年猫身上进行。在损伤后4 - 5周,通过细胞外注射神经生物素对C3中的CINs进行染色。通过轴突生长相关蛋白-43(GAP-43)的免疫反应性来识别被轴突切断的CINs的胞体。近一半的CINs有从远端树突长出的新生轴突。这些轴突对树突蛋白微管相关蛋白2a/b(MAP2a/b)缺乏免疫反应性;一些有GAP-43免疫反应性终末;几乎所有轴突都具有典型的轴突形态特征。其他CINs的树突没有产生新生轴突。然而,这些CINs每个都有一个直接从胞体或非常近端的树突伸出的长轴突样突起(L-ALP)。L-ALP缺乏MAP2a/b免疫反应性。其中一些L-ALP穿过损伤部位并形成纽扣样肿胀。这些结果表明,近端被轴突切断的脊髓中间神经元有潜力通过从远端树突长出的新生轴突形成新的连接。其他神经元可能能够使其原始轴突再生。