Combination of gonadal steroid treatment and peripheral nerve grafting results in a peripheral motoneuron-like pattern of BII-tubulin mRNA expression in axotomized hamster rubrospinal motoneurons

Paul D. Storer, John D. Houle, Monica Oblinger, Kathryn Jones

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Rubrospinal motoneurons (RSMN) represent a population of androgen receptor-containing central motoneurons in rodents. In this study, the ability of testosterone propionate (TP), alone or in conjunction with a peripheral nerve graft (PNG), to alter the molecular program of injured RSMN was accomplished using βII-tubulin cDNA probes and quantitative in situ hybridization (ISH). Initial fluoro-gold labeling experiments following a T1 hemisection established that, as in the rat, the hamster rubrospinal system is essentially crossed and that injured RSMN concentrate in the ventrolateral region of the red nucleus. In the second experimental series, adult gonadectomized male hamsters were subjected to a right T1 hemisection, with half of the operated animals immediately subcutaneously implanted with 1 10 mm TP Silastic capsule and the other half sham implanted. In a third experimental series, animals were subjected to T1 hemisection, followed by transplantation of a predegenerated autologous segment of peripheral nerve. Half of the animals in each group received TP implants at the time of spinal cord injury and PNG. Postoperative times were 2, 7, and 14 days (dpo). Quantitative ISH was performed using a βII-tubulin-specific 33P-labeled cDNA probe, emulsion autoradiography, and computerized image analysis for grain counting. Injury alone resulted in a short-lived increase in βII-tubulin mRNA expression in the RSMN at 2 dpo, with a significant decline to well below control values at 7 and 14 dpo. TP treatment or PNG alone attenuated, but did not prevent, the down-regulation of βII-tubulin mRNA. In contrast, the combination of TP with a PNG sustained the injury-induced increase in βII-tubulin mRNA levels throughout the postoperative period of 2, 7, and 14 dpo. The synergistic effects of the two treatment strategies confirm the importance of targeting multiple aspects of the injury response for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)364-373
Number of pages10
JournalJournal of Comparative Neurology
Volume449
Issue number4
DOIs
StatePublished - Aug 5 2002
Externally publishedYes

Fingerprint

Testosterone Propionate
Motor Neurons
Tubulin
Peripheral Nerves
Cricetinae
Steroids
Messenger RNA
Transplants
In Situ Hybridization
Complementary DNA
Red Nucleus
Multiple Trauma
Wounds and Injuries
Androgen Receptors
Emulsions
Autoradiography
Spinal Cord Injuries
Postoperative Period
Capsules
Rodentia

Keywords

  • In situ hybridization
  • Red nucleus
  • Spinal cord injury
  • Testosterone

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Combination of gonadal steroid treatment and peripheral nerve grafting results in a peripheral motoneuron-like pattern of BII-tubulin mRNA expression in axotomized hamster rubrospinal motoneurons",
abstract = "Rubrospinal motoneurons (RSMN) represent a population of androgen receptor-containing central motoneurons in rodents. In this study, the ability of testosterone propionate (TP), alone or in conjunction with a peripheral nerve graft (PNG), to alter the molecular program of injured RSMN was accomplished using βII-tubulin cDNA probes and quantitative in situ hybridization (ISH). Initial fluoro-gold labeling experiments following a T1 hemisection established that, as in the rat, the hamster rubrospinal system is essentially crossed and that injured RSMN concentrate in the ventrolateral region of the red nucleus. In the second experimental series, adult gonadectomized male hamsters were subjected to a right T1 hemisection, with half of the operated animals immediately subcutaneously implanted with 1 10 mm TP Silastic capsule and the other half sham implanted. In a third experimental series, animals were subjected to T1 hemisection, followed by transplantation of a predegenerated autologous segment of peripheral nerve. Half of the animals in each group received TP implants at the time of spinal cord injury and PNG. Postoperative times were 2, 7, and 14 days (dpo). Quantitative ISH was performed using a βII-tubulin-specific 33P-labeled cDNA probe, emulsion autoradiography, and computerized image analysis for grain counting. Injury alone resulted in a short-lived increase in βII-tubulin mRNA expression in the RSMN at 2 dpo, with a significant decline to well below control values at 7 and 14 dpo. TP treatment or PNG alone attenuated, but did not prevent, the down-regulation of βII-tubulin mRNA. In contrast, the combination of TP with a PNG sustained the injury-induced increase in βII-tubulin mRNA levels throughout the postoperative period of 2, 7, and 14 dpo. The synergistic effects of the two treatment strategies confirm the importance of targeting multiple aspects of the injury response for therapeutic intervention.",
keywords = "In situ hybridization, Red nucleus, Spinal cord injury, Testosterone",
author = "Storer, {Paul D.} and Houle, {John D.} and Monica Oblinger and Kathryn Jones",
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T1 - Combination of gonadal steroid treatment and peripheral nerve grafting results in a peripheral motoneuron-like pattern of BII-tubulin mRNA expression in axotomized hamster rubrospinal motoneurons

AU - Storer, Paul D.

AU - Houle, John D.

AU - Oblinger, Monica

AU - Jones, Kathryn

PY - 2002/8/5

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N2 - Rubrospinal motoneurons (RSMN) represent a population of androgen receptor-containing central motoneurons in rodents. In this study, the ability of testosterone propionate (TP), alone or in conjunction with a peripheral nerve graft (PNG), to alter the molecular program of injured RSMN was accomplished using βII-tubulin cDNA probes and quantitative in situ hybridization (ISH). Initial fluoro-gold labeling experiments following a T1 hemisection established that, as in the rat, the hamster rubrospinal system is essentially crossed and that injured RSMN concentrate in the ventrolateral region of the red nucleus. In the second experimental series, adult gonadectomized male hamsters were subjected to a right T1 hemisection, with half of the operated animals immediately subcutaneously implanted with 1 10 mm TP Silastic capsule and the other half sham implanted. In a third experimental series, animals were subjected to T1 hemisection, followed by transplantation of a predegenerated autologous segment of peripheral nerve. Half of the animals in each group received TP implants at the time of spinal cord injury and PNG. Postoperative times were 2, 7, and 14 days (dpo). Quantitative ISH was performed using a βII-tubulin-specific 33P-labeled cDNA probe, emulsion autoradiography, and computerized image analysis for grain counting. Injury alone resulted in a short-lived increase in βII-tubulin mRNA expression in the RSMN at 2 dpo, with a significant decline to well below control values at 7 and 14 dpo. TP treatment or PNG alone attenuated, but did not prevent, the down-regulation of βII-tubulin mRNA. In contrast, the combination of TP with a PNG sustained the injury-induced increase in βII-tubulin mRNA levels throughout the postoperative period of 2, 7, and 14 dpo. The synergistic effects of the two treatment strategies confirm the importance of targeting multiple aspects of the injury response for therapeutic intervention.

AB - Rubrospinal motoneurons (RSMN) represent a population of androgen receptor-containing central motoneurons in rodents. In this study, the ability of testosterone propionate (TP), alone or in conjunction with a peripheral nerve graft (PNG), to alter the molecular program of injured RSMN was accomplished using βII-tubulin cDNA probes and quantitative in situ hybridization (ISH). Initial fluoro-gold labeling experiments following a T1 hemisection established that, as in the rat, the hamster rubrospinal system is essentially crossed and that injured RSMN concentrate in the ventrolateral region of the red nucleus. In the second experimental series, adult gonadectomized male hamsters were subjected to a right T1 hemisection, with half of the operated animals immediately subcutaneously implanted with 1 10 mm TP Silastic capsule and the other half sham implanted. In a third experimental series, animals were subjected to T1 hemisection, followed by transplantation of a predegenerated autologous segment of peripheral nerve. Half of the animals in each group received TP implants at the time of spinal cord injury and PNG. Postoperative times were 2, 7, and 14 days (dpo). Quantitative ISH was performed using a βII-tubulin-specific 33P-labeled cDNA probe, emulsion autoradiography, and computerized image analysis for grain counting. Injury alone resulted in a short-lived increase in βII-tubulin mRNA expression in the RSMN at 2 dpo, with a significant decline to well below control values at 7 and 14 dpo. TP treatment or PNG alone attenuated, but did not prevent, the down-regulation of βII-tubulin mRNA. In contrast, the combination of TP with a PNG sustained the injury-induced increase in βII-tubulin mRNA levels throughout the postoperative period of 2, 7, and 14 dpo. The synergistic effects of the two treatment strategies confirm the importance of targeting multiple aspects of the injury response for therapeutic intervention.

KW - In situ hybridization

KW - Red nucleus

KW - Spinal cord injury

KW - Testosterone

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U2 - 10.1002/cne.10304

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