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A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord.

ABSTRACT: CNS lesions induce production of ECM molecules that inhibit axon regeneration. One major inhibitory family is the chondroitin sulfate proteoglycans (CSPGs). Reduction of their glycosaminoglycan (GAG) chains with chondroitinase ABC leads to increased axon regeneration that does not extend well past the lesion. Chondroitinase ABC, however, is unable to completely digest the GAG chains from the protein core, leaving an inhibitory "stub" carbohydrate behind. We used a newly designed DNA enzyme, which targets the mRNA of a critical enzyme that initiates glycosylation of the protein backbone of PGs, xylosyltransferase-1. DNA enzyme administration to TGF-beta-stimulated astrocytes in culture reduced specific GAG chains. The same DNA enzyme applied to the injured spinal cord led to a strong reduction of the GAG chains in the lesion penumbra and allowed axons to regenerate around the core of the lesion. Our experiments demonstrate the critical role of PGs, and particularly those in the penumbra, in causing regeneration failure in the adult spinal cord.

SUBMITTER: Grimpe B

PROVIDER: S-EPMC6730336 | biostudies-literature | 2004 Feb

REPOSITORIES: biostudies-literature

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A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord.

Grimpe Barbara B Silver Jerry J

The Journal of neuroscience : the official journal of the Society for Neuroscience 20040201 6

CNS lesions induce production of ECM molecules that inhibit axon regeneration. One major inhibitory family is the chondroitin sulfate proteoglycans (CSPGs). Reduction of their glycosaminoglycan (GAG) chains with chondroitinase ABC leads to increased axon regeneration that does not extend well past the lesion. Chondroitinase ABC, however, is unable to completely digest the GAG chains from the protein core, leaving an inhibitory "stub" carbohydrate behind. We used a newly designed DNA enzyme, whic ...[more]

PMID: 14960611

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Project description:Satellite glial cells (SGCs) of the dorsal root ganglia (DRG) ensure homeostasis and proportional excitability of sensory neurons and gained interest in the field of development and maintenance of neuropathic pain. Pigs represent a suitable species for translational medicine with a more similar anatomy and physiology to humans compared to rodents, and are used in research regarding treatment of neuropathic pain. Knowledge of anatomical and physiological features of porcine SGCs is prerequisite for interpreting potential alterations. However, state of knowledge is still limited. In the present study, light microscopy, ultrastructural analysis and immunofluorescence staining was performed. SGCs tightly surround DRG neurons with little vascularized connective tissue between SGC-neuron units, containing, among others, axons and Schwann cells. DRG were mainly composed of large sized neurons (∼59%), accompanied by fewer medium sized (∼36%) and small sized sensory neurons (∼6%). An increase of neuronal body size was concomitant with an increased number of surrounding SGCs. The majority of porcine SGCs expressed glutamine synthetase and inwardly rectifying potassium channel Kir 4.1, known as SGC-specific markers in other species. Similar to canine SGCs, marked numbers of porcine SGCs were immunopositive for glial fibrillary acidic protein, 2',3'-cyclic-nucleotide 3'-phosphodiesterase and the transcription factor Sox2. Low to moderate numbers of SGCs showed aquaporin 4-immunoreactivity (AQP4) as described for murine SGCs. AQP4-immunoreactivity was primarily found in SGCs ensheathing small and medium sized neuronal somata. Low numbers of SGCs were immunopositive for ionized calcium-binding adapter molecule 1, indicating a potential immune cell character. No immunoreactivity for common leukocyte antigen CD45 nor neural/glial antigen 2 was detected. The present study provides essential insights into the characteristic features of non-activated porcine SGCs, contributing to a better understanding of this cell population and its functional aspects. This will help to interpret possible changes that might occur under activating conditions such as pain.

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Dataset Information

A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord.

Publications

A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord.

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