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Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression
Major depressive disorder (MDD) is a major cause of disability in adults. MDD is both a comorbidity and a risk factor for Alzheimer’s disease (AD), and regular physical exercise has been associated with reduced incidence and severity of MDD and AD. Irisin is an exercise-induced myokine derived from...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Society for Neuroscience
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927507/ https://www.ncbi.nlm.nih.gov/pubmed/36697257 http://dx.doi.org/10.1523/ENEURO.0256-22.2023 |
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author | Lima-Filho, Ricardo Fortuna, Juliana S. Cozachenco, Danielle Isaac, Alinny R. Lyra e Silva, Natalia Saldanha, Alice Santos, Luis E. Ferreira, Sergio T. Lourenco, Mychael V. De Felice, Fernanda G. |
author_facet | Lima-Filho, Ricardo Fortuna, Juliana S. Cozachenco, Danielle Isaac, Alinny R. Lyra e Silva, Natalia Saldanha, Alice Santos, Luis E. Ferreira, Sergio T. Lourenco, Mychael V. De Felice, Fernanda G. |
author_sort | Lima-Filho, Ricardo |
collection | PubMed |
description | Major depressive disorder (MDD) is a major cause of disability in adults. MDD is both a comorbidity and a risk factor for Alzheimer’s disease (AD), and regular physical exercise has been associated with reduced incidence and severity of MDD and AD. Irisin is an exercise-induced myokine derived from proteolytic processing of fibronectin type III domain-containing protein 5 (FNDC5). FNDC5/irisin is reduced in the brains of AD patients and mouse models. However, whether brain FNDC5/irisin expression is altered in depression remains elusive. Here, we investigate changes in fndc5 expression in postmortem brain tissue from MDD individuals and mouse models of depression. We found decreased fndc5 expression in the MDD prefrontal cortex, both with and without psychotic traits. We further demonstrate that the induction of depressive-like behavior in male mice by lipopolysaccharide decreased fndc5 expression in the frontal cortex, but not in the hippocampus. Conversely, chronic corticosterone administration increased fndc5 expression in the frontal cortex, but not in the hippocampus. Social isolation in mice did not result in altered fndc5 expression in either frontal cortex or hippocampus. Finally, fluoxetine, but not other antidepressants, increased fndc5 gene expression in the mouse frontal cortex. Results indicate a region-specific modulation of fndc5 in depressive-like behavior and by antidepressant in mice. Our finding of decreased prefrontal cortex fndc5 expression in MDD individuals differs from results in mice, highlighting the importance of carefully interpreting observations in mice. The reduction in fndc5 mRNA suggests that decreased central FNDC5/irisin could comprise a shared pathologic mechanism between MDD and AD. |
format | Online Article Text |
id | pubmed-9927507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Society for Neuroscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-99275072023-02-16 Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression Lima-Filho, Ricardo Fortuna, Juliana S. Cozachenco, Danielle Isaac, Alinny R. Lyra e Silva, Natalia Saldanha, Alice Santos, Luis E. Ferreira, Sergio T. Lourenco, Mychael V. De Felice, Fernanda G. eNeuro Research Article: New Research Major depressive disorder (MDD) is a major cause of disability in adults. MDD is both a comorbidity and a risk factor for Alzheimer’s disease (AD), and regular physical exercise has been associated with reduced incidence and severity of MDD and AD. Irisin is an exercise-induced myokine derived from proteolytic processing of fibronectin type III domain-containing protein 5 (FNDC5). FNDC5/irisin is reduced in the brains of AD patients and mouse models. However, whether brain FNDC5/irisin expression is altered in depression remains elusive. Here, we investigate changes in fndc5 expression in postmortem brain tissue from MDD individuals and mouse models of depression. We found decreased fndc5 expression in the MDD prefrontal cortex, both with and without psychotic traits. We further demonstrate that the induction of depressive-like behavior in male mice by lipopolysaccharide decreased fndc5 expression in the frontal cortex, but not in the hippocampus. Conversely, chronic corticosterone administration increased fndc5 expression in the frontal cortex, but not in the hippocampus. Social isolation in mice did not result in altered fndc5 expression in either frontal cortex or hippocampus. Finally, fluoxetine, but not other antidepressants, increased fndc5 gene expression in the mouse frontal cortex. Results indicate a region-specific modulation of fndc5 in depressive-like behavior and by antidepressant in mice. Our finding of decreased prefrontal cortex fndc5 expression in MDD individuals differs from results in mice, highlighting the importance of carefully interpreting observations in mice. The reduction in fndc5 mRNA suggests that decreased central FNDC5/irisin could comprise a shared pathologic mechanism between MDD and AD. Society for Neuroscience 2023-02-13 /pmc/articles/PMC9927507/ /pubmed/36697257 http://dx.doi.org/10.1523/ENEURO.0256-22.2023 Text en Copyright © 2023 Lima-Filho et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article: New Research Lima-Filho, Ricardo Fortuna, Juliana S. Cozachenco, Danielle Isaac, Alinny R. Lyra e Silva, Natalia Saldanha, Alice Santos, Luis E. Ferreira, Sergio T. Lourenco, Mychael V. De Felice, Fernanda G. Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression |
title | Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression |
title_full | Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression |
title_fullStr | Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression |
title_full_unstemmed | Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression |
title_short | Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression |
title_sort | brain fndc5/irisin expression in patients and mouse models of major depression |
topic | Research Article: New Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927507/ https://www.ncbi.nlm.nih.gov/pubmed/36697257 http://dx.doi.org/10.1523/ENEURO.0256-22.2023 |
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