Characterization of spinal motoneuron degeneration following different types of peripheral nerve injury in neonatal and adult mice

Abstract

Experimental lesions have been used widely to induce motoneuron (MN) degeneration as a model to test the ability of different trophic molecules to prevent lesion-induced alterations. However, the morphological mechanisms of spinal MN death following different types of lesions is not clear at the present time. In this study, we have characterized the morphological characteristics of MN cell death by examining DNA fragmentation and the ultrastructural and light microscopic morphological features of MNs following different types of spinal nerve injury (i.e., axotomy and avulsion) in the developing and adult mouse. In neonatal mice, axotomy induced cell death as well as the atrophy of MNs that survived the injury. DNA fragmentation could be detected by using the terminal deoxynucleotidyl transferase (TUNEL) method during the cell death process following neonatal axotomy, whereas TUNEL labeling was not observed following either neonatal or adult avulsion. However, with the exception of TUNEL labeling, the morphological characteristics of MN death following neonatal axotomy and avulsion were similar, and both resembled most closely the form of programmed cell death termed cytoplasmic or type 3B, which exhibits similarities as well as differences with currently accepted definitions of apoptosis. By contrast, adult avulsion resulted in a type of degeneration that resembled necrosis more closely. However, even there, the morphology was mixed, showing characteristics of both apoptosis and necrosis. These results indicate that the mode of MN degeneration is complex and is related to developmental age and type of lesion.

Induction of endogenous neural precursors in mouse models of spinal cord injury and disease

“…This finding suggests that a unilateral and relatively distal axotomy of spinal motoneurons in adult mice is an insufficient stimulus (Pollin et al. , 1991; Li et al. , 1998; Kong and Xu, 1999) to activate a significant NPC response.…”

Adenoviral gene transfer of GDNF, BDNF and TGFβ2, but not CNTF, cardiotrophin‐1 or IGF1, protects injured adult motoneurons after facial nerve avulsion

“…The precise mechanism of adult motoneuron death after peripheral nerve avulsion remains unclear. Some investigators reported that the degeneration of motoneurons following avulsion is due to apoptosis (Martin et al, 1999; Martin and Liu, 2002), whereas others described that it more closely resembles necrosis (Li et al, 1998). Herpes simplex virus vector‐mediated expression of Bcl‐2 protected spinal motor neurons from degeneration following root avulsion (Yamada et al, 2001), whereas caspase inhibitors failed to rescue avulsed motoneurons in adult rats (Chan et al, 2001), suggesting that adult motoneuron death after avulsion is not merely due to an apoptotic mechanism.…”

Intertwined pathways of programmed cell death in immunity

“…This form of cell death has since been explicitly reported in many examples of developmental PCD (101–106), and perhaps the most medically relevant example arises from ischemia‐reperfusion events that result in the opening of the mitochondrial permeability transition pore (mPTP) (107). Components of the mPTP were thought to include the voltage‐dependent anion channel (VDAC), the adenine nucleotide translocator (ANT), the peptidyl‐prolyl cis‐trans isomerase, cyclophilin D, and other molecules (108); however, only cyclophilin D has been verified by genetic ablation experiments (109).…”