Improved sciatic nerve regeneration by local thyroid hormone treatment in adult rat is accompanied by increased expression of SCG10

Thyroid hormone plays an important role in regulating the development and regeneration of the nervous system. Our previous work showed that local administration of triiodothyronine (T3) at the level of transected rat sciatic nerve increased the number and diameter of regenerated axons, but the mecha...

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Published in:	Experimental neurology Vol. 197; no. 1; pp. 258 - 267
Main Authors:	Voria, I., Hauser, J., Axis, A., Schenker, M., Bichet, S., Kuntzer, T., Grenningloh, G., Barakat-Walter, I.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Inc 2006 Elsevier
Subjects:	Animals Biological and medical sciences Blotting, Western Carrier Proteins Cranial nerves. Peripheral nerves. Autonomic nervous system Dorsal root ganglia Ganglia, Spinal - drug effects Ganglia, Spinal - metabolism Growth-associated protein Immunohistochemistry In Situ Hybridization Injuries of the nervous system and the skull. Diseases due to physical agents Male Medical sciences Membrane Proteins Microtubules Nerve Growth Factors - biosynthesis Nerve Regeneration - drug effects Nerve Tissue Proteins - biosynthesis Neurosurgery Peripheral nerve regeneration Rats Rats, Wistar RNA, Messenger - biosynthesis RNA, Messenger - genetics SCG10 Sciatic nerve Sciatic Nerve - cytology Sciatic Nerve - drug effects Sciatic Nerve - physiology Silicone nerve guide tubes Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Thyroid Hormones - pharmacology Traumas. Diseases due to physical agents Triiodothyronine (T3) Triiodothyronine - pharmacology Up-Regulation - drug effects Dorsal root ganglia Peripheral nerve regeneration Microtubules SCG10 Growth-associated protein Triiodothyronine (T3) In situ hybridization Sciatic nerve Silicone nerve guide tubes Immunohistochemistry Phosphates Peripheral nerve Spinal cord Rat Growth Central nervous system Nervous system Growth cone Local administration Surgery Immunoblotting assay Quantitative analysis Implant Rodentia Axon Protein Regeneration Vertebrata Mammalia Neuron Treatment Animal Cytoskeleton Thyroid hormone Spinal ganglion Microtubule
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Summary:	Thyroid hormone plays an important role in regulating the development and regeneration of the nervous system. Our previous work showed that local administration of triiodothyronine (T3) at the level of transected rat sciatic nerve increased the number and diameter of regenerated axons, but the mechanism underlying the improved regeneration is still unclear. Here, we have investigated the effect of T3 on the expression of SCG10, a regulator of microtubule dynamics in growth cones. After transection of adult rat sciatic nerves, silicone tubes were implanted and filled with T3 or phosphate-buffered solution. At various time points following surgery, the expression of SCG10 protein and mRNA was analyzed. Semi-quantitative Western blot analysis revealed that sciatic nerve transection induced a more than 20-fold upregulation of SCG10 protein in proximal nerve segments at 1 day post-lesion, while at this time point, SCG10 mRNA in dorsal root ganglion neurons was not increased yet. The increase in SCG10 protein and mRNA could be observed over 30 days. Local T3 treatment significantly enhanced the increase in SCG10 protein levels about two-fold in the different segments of transected nerve during the regeneration period. Also SCG10 mRNA levels in lumbar ganglia were enhanced. Immunohistochemical analysis showed that T3 treatment not only increased the number of SCG10 positive axons but also the intensity of their staining. These results suggest that SCG10 is involved in the regulation of regeneration. The stimulating effect of T3 on SCG10 expression could provide a mechanism by which T3 enhances peripheral nerve regeneration.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-4886 1090-2430
DOI:	10.1016/j.expneurol.2005.10.001