Abstract
BackgroundThe spinal cord is limited in its capacity to repair after damage caused by injury or disease. However, propriospinal (PS) neurons in the spinal cord have demonstrated a propensity for axonal regeneration after spinal cord injury. They can regrow and extend axonal projections to re-establish connections across a spinal lesion. We have previously reported differential reactions of two distinct PS neuronal populations—short thoracic propriospinal (TPS) and long descending propriospinal tract (LDPT) neurons—following a low thoracic (T10) spinal cord injury in a rat model. Immediately after injury, TPS neurons undergo a strong initial regenerative response, defined by the upregulation of transcripts to several growth factor receptors, and growth associated proteins. Many also initiate a strong apoptotic response, leading to cell death. LDPT neurons, on the other hand, show neither a regenerative nor an apoptotic response. They show either a lowered expression or no change in genes for a variety of growth associated proteins, and these neurons survive for at least 2 months post-axotomy. There are several potential explanations for this lack of cellular response for LDPT neurons, one of which is the distance of the LDPT cell body from the T10 lesion. In this study, we examined the molecular response of LDPT neurons to axotomy caused by a proximal spinal cord lesion.ResultsUtilizing laser capture microdissection and RNA quantification with branched DNA technology, we analyzed the change in gene expression in LDPT neurons following axotomy near their cell body. Expression patterns of 34 genes selected for their robust responses in TPS neurons were analyzed 3 days following a T2 spinal lesion. Our results show that after axonal injury nearer their cell bodies, there was a differential response of the same set of genes evaluated previously in TPS neurons after proximal axotomy, and LDPT neurons after distal axotomy (T10 spinal transection). The genetic response was much less robust than for TPS neurons after proximal axotomy, included both increased and decreased expression of certain genes, and did not suggest either a major regenerative or apoptotic response within the population of genes examined.ConclusionsThe data collectively demonstrate that the location of axotomy in relation to the soma of a neuron has a major effect on its ability to mount a regenerative response. However, the data also suggest that there are endogenous differences in the LDPT and TPS neuronal populations that affect their response to axotomy. These phenotypic differences may indicate that different or multiple therapies may be needed following spinal cord injury to stimulate maximal regeneration of all PS axons.
Highlights
The spinal cord is limited in its capacity to repair after damage caused by injury or disease
The analysis in this study was focused on the response of specific genes which had significantly changed in the long descending propriospinal tract (LDPT) or thoracic propriospinal (TPS) populations after thoracic lesions in previous studies (Table 1; 17, 18)
The genes chosen for analysis were previously found to be significantly up or down-regulated 3-days post injury in LDPT and/or TPS neurons following gene expression and qRT PCR array analyses [17, 18]
Summary
The spinal cord is limited in its capacity to repair after damage caused by injury or disease. Propriospinal (PS) neurons in the spinal cord have demonstrated a propensity for axonal regeneration after spinal cord injury. The motor and sensory impairments that accompany injuries to the spinal cord are largely irreversible due to the inability of supraspinal neuronal populations, including the corticospinal (CST) and rubrospinal (RuST) tracts, to undergo a sustained regenerative response that can re-establish long distance connections [1, 2]. Short thoracic PS neurons arise in the thoracic spinal cord and their axons ascend or descend one or two spinal levels. This PS population has an important role in controlling postural mechanisms and axial musculature. These two classes of propriospinal neurons work together with supraspinal neurons modulating and honing locomotor ability, coordination of the extremities, and postural support [14, 15]
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