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Acute Leptin Treatment Enhances Functional Recovery after Spinal Cord Injury
BACKGROUND: Spinal cord injury is a major cause of long-term disability and has no current clinically accepted treatment. Leptin, an adipocyte-derived hormone, is best known as a regulator of food intake and energy expenditure. Interestingly, several studies have demonstrated that leptin has signifi...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334982/ https://www.ncbi.nlm.nih.gov/pubmed/22536415 http://dx.doi.org/10.1371/journal.pone.0035594 |
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author | Fernández-Martos, Carmen María González, Pau Rodriguez, Francisco Javier |
author_facet | Fernández-Martos, Carmen María González, Pau Rodriguez, Francisco Javier |
author_sort | Fernández-Martos, Carmen María |
collection | PubMed |
description | BACKGROUND: Spinal cord injury is a major cause of long-term disability and has no current clinically accepted treatment. Leptin, an adipocyte-derived hormone, is best known as a regulator of food intake and energy expenditure. Interestingly, several studies have demonstrated that leptin has significant effects on proliferation and cell survival in different neuropathologies. Here, we sought to evaluate the role of leptin after spinal cord injury. FINDINGS: Based on its proposed neuroprotective role, we have evaluated the effects of a single, acute intraparenchymal injection of leptin in a clinically relevant animal model of spinal cord injury. As determined by quantitative Real Time-PCR, endogenous leptin and the long isoform of the leptin receptor genes show time-dependent variations in their expression in the healthy and injured adult spinal cord. Immunohistochemical analysis of post-injury tissue showed the long isoform of the leptin receptor expression in oligodendrocytes and, to a lesser extent, in astrocytes, microglia/macrophages and neurons. Moreover, leptin administered after spinal cord injury increased the expression of neuroprotective genes, reduced caspase-3 activity and decreased the expression of pro-inflammatory molecules. In addition, histological analysis performed at the completion of the study showed that leptin treatment reduced microglial reactivity and increased caudal myelin preservation, but it did not modulate astroglial reactivity. Consequently, leptin improved the recovery of sensory and locomotor functioning. CONCLUSIONS: Our data suggest that leptin has a prominent neuroprotective and anti-inflammatory role in spinal cord damage and highlights leptin as a promising therapeutic agent. |
format | Online Article Text |
id | pubmed-3334982 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33349822012-04-25 Acute Leptin Treatment Enhances Functional Recovery after Spinal Cord Injury Fernández-Martos, Carmen María González, Pau Rodriguez, Francisco Javier PLoS One Research Article BACKGROUND: Spinal cord injury is a major cause of long-term disability and has no current clinically accepted treatment. Leptin, an adipocyte-derived hormone, is best known as a regulator of food intake and energy expenditure. Interestingly, several studies have demonstrated that leptin has significant effects on proliferation and cell survival in different neuropathologies. Here, we sought to evaluate the role of leptin after spinal cord injury. FINDINGS: Based on its proposed neuroprotective role, we have evaluated the effects of a single, acute intraparenchymal injection of leptin in a clinically relevant animal model of spinal cord injury. As determined by quantitative Real Time-PCR, endogenous leptin and the long isoform of the leptin receptor genes show time-dependent variations in their expression in the healthy and injured adult spinal cord. Immunohistochemical analysis of post-injury tissue showed the long isoform of the leptin receptor expression in oligodendrocytes and, to a lesser extent, in astrocytes, microglia/macrophages and neurons. Moreover, leptin administered after spinal cord injury increased the expression of neuroprotective genes, reduced caspase-3 activity and decreased the expression of pro-inflammatory molecules. In addition, histological analysis performed at the completion of the study showed that leptin treatment reduced microglial reactivity and increased caudal myelin preservation, but it did not modulate astroglial reactivity. Consequently, leptin improved the recovery of sensory and locomotor functioning. CONCLUSIONS: Our data suggest that leptin has a prominent neuroprotective and anti-inflammatory role in spinal cord damage and highlights leptin as a promising therapeutic agent. Public Library of Science 2012-04-20 /pmc/articles/PMC3334982/ /pubmed/22536415 http://dx.doi.org/10.1371/journal.pone.0035594 Text en Fernández-Martos et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Fernández-Martos, Carmen María González, Pau Rodriguez, Francisco Javier Acute Leptin Treatment Enhances Functional Recovery after Spinal Cord Injury |
title | Acute Leptin Treatment Enhances Functional Recovery after Spinal Cord Injury |
title_full | Acute Leptin Treatment Enhances Functional Recovery after Spinal Cord Injury |
title_fullStr | Acute Leptin Treatment Enhances Functional Recovery after Spinal Cord Injury |
title_full_unstemmed | Acute Leptin Treatment Enhances Functional Recovery after Spinal Cord Injury |
title_short | Acute Leptin Treatment Enhances Functional Recovery after Spinal Cord Injury |
title_sort | acute leptin treatment enhances functional recovery after spinal cord injury |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334982/ https://www.ncbi.nlm.nih.gov/pubmed/22536415 http://dx.doi.org/10.1371/journal.pone.0035594 |
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