Dataset Information

Expression of the regeneration-associated protein SPRR1A in primary sensory neurons and spinal cord of the adult mouse following peripheral and central injury.

ABSTRACT: Small proline-rich repeat protein 1A (SPRR1A) is expressed in dorsal root ganglion (DRG) neurons following peripheral nerve injury but it is not known whether SPRR1A is differentially expressed following injury to peripheral versus central DRG projections and a detailed characterization of expression in sensory neuron subpopulations and spinal cord has not been performed. Here we use immunocytochemical techniques to characterize SPRR1A expression following sciatic nerve, dorsal root, and dorsal column injury in adult mice. SPRR1A was not detected in naïve spinal cord, DRG, or peripheral nerves and there was minimal expression following injury to the centrally projecting branches of DRG neurons. However, following peripheral (sciatic) nerve injury, intense SPRR1A immunoreactivity was observed in the dorsal horn and motoneurons of the spinal cord, in L4/5 DRG neurons, and in the injured nerve. A time-course study comparing expression following sciatic nerve crush and transection revealed maximum SPRR1A levels at day 7 in both models. However, while SPRR1A was downregulated to baseline by 30 days postlesion following crush injury, it remained elevated 30 days after transection. Cell-size and double-labeling studies revealed that SPRR1A was expressed by DRG cells of all sizes and colocalized with classical markers of DRG subpopulations and their primary afferent terminals. High coexpression of SPRR1A with activating transcription factor-3 and growth-associated protein-43 was observed, indicating that it is expressed by injured and regenerating neurons. This study supports the hypothesis that SPRR1A is a regeneration-associated gene and that SPRR1A provides a valuable marker to assess the regenerative potential of injured neurons.

SUBMITTER: Starkey ML

PROVIDER: S-EPMC3339437 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Publications

Expression of the regeneration-associated protein SPRR1A in primary sensory neurons and spinal cord of the adult mouse following peripheral and central injury.

Starkey Michelle L ML Davies Meirion M Yip Ping K PK Carter Lucy M LM Wong Danny J N DJ McMahon Stephen B SB Bradbury Elizabeth J EJ

The Journal of comparative neurology 20090301 1

Small proline-rich repeat protein 1A (SPRR1A) is expressed in dorsal root ganglion (DRG) neurons following peripheral nerve injury but it is not known whether SPRR1A is differentially expressed following injury to peripheral versus central DRG projections and a detailed characterization of expression in sensory neuron subpopulations and spinal cord has not been performed. Here we use immunocytochemical techniques to characterize SPRR1A expression following sciatic nerve, dorsal root, and dorsal ...[more]

PMID: 19107756

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Project description:Directing the organization of cells into a tissue with defined architectures is one use of biomaterials for regenerative medicine. To this end, hydrogels are widely investigated as they have mechanical properties similar to native soft tissues and can be formed in situ to conform to a defect. Herein, we describe the development of porous hydrogel tubes fabricated through a two-step polymerization process with an intermediate microsphere phase that provides macroscale porosity (66.5%) for cell infiltration. These tubes were investigated in a spinal cord injury model, with the tubes assembled to conform to the injury and to provide an orientation that guides axons through the injury. Implanted tubes had good apposition and were integrated with the host tissue due to cell infiltration, with a transient increase in immune cell infiltration at 1?week that resolved by 2?weeks post injury compared to a gelfoam control. The glial scar was significantly reduced relative to control, which enabled robust axon growth along the inner and outer surface of the tubes. Axon density within the hydrogel tubes (1744 axons/mm2) was significantly increased more than 3-fold compared to the control (456 axons/mm2), with approximately 30% of axons within the tube myelinated. Furthermore, implantation of hydrogel tubes enhanced functional recovery relative to control. This modular assembly of porous tubes to fill a defect and directionally orient tissue growth could be extended beyond spinal cord injury to other tissues, such as vascular or musculoskeletal tissue. STATEMENT OF SIGNIFICANCE: Tissue engineering approaches that mimic the native architecture of healthy tissue are needed following injury. Traditionally, pre-molded scaffolds have been implemented but require a priori knowledge of wound geometries. Conversely, hydrogels can conform to any injury, but do not guide bi-directional regeneration. In this work, we investigate the feasibility of a system of modular hydrogel tubes to promote bi-directional regeneration after spinal cord injury. This system allows for tubes to be cut to size during surgery and implanted one-by-one to fill any injury, while providing bi-directional guidance. Moreover, this system of tubes can be broadly applied to tissue engineering approaches that require a modular guidance system, such as repair to vascular or musculoskeletal tissues.

Project description:BACKGROUND: Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. RESULTS: Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. CONCLUSIONS: This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability.

Dataset Information

Expression of the regeneration-associated protein SPRR1A in primary sensory neurons and spinal cord of the adult mouse following peripheral and central injury.

Publications

Expression of the regeneration-associated protein SPRR1A in primary sensory neurons and spinal cord of the adult mouse following peripheral and central injury.

Similar Datasets

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