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Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and Hypothyroidism

The clinical effectiveness of supportive therapy with thyroid hormones in drug-resistant depression is well-known; however, the mechanisms of action of these hormones in the adult brain have not been fully elucidated to date. We determined the effects of venlafaxine and/or L-thyroxine on metabolic p...

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Autores principales: Głombik, Katarzyna, Detka, Jan, Budziszewska, Bogusława
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227539/
https://www.ncbi.nlm.nih.gov/pubmed/34198731
http://dx.doi.org/10.3390/cells10061394
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author Głombik, Katarzyna
Detka, Jan
Budziszewska, Bogusława
author_facet Głombik, Katarzyna
Detka, Jan
Budziszewska, Bogusława
author_sort Głombik, Katarzyna
collection PubMed
description The clinical effectiveness of supportive therapy with thyroid hormones in drug-resistant depression is well-known; however, the mechanisms of action of these hormones in the adult brain have not been fully elucidated to date. We determined the effects of venlafaxine and/or L-thyroxine on metabolic parameters and markers involved in the regulation of synaptic plasticity and cell damage in an animal model of coexisting depression and hypothyroidism, namely, Wistar Kyoto rats treated with propylthiouracil. In this model, in relation to the depression model itself, the glycolysis process in the brain was weakened, and a reduction in pyruvate dehydrogenase in the frontal cortex was normalized only by the combined treatment with L-thyroxine and venlafaxine, whereas changes in pyruvate and lactate levels were affected by all applied therapies. None of the drugs improved the decrease in the expression of mitochondrial respiratory chain enzymes. No intensification of glucocorticoid action was shown, while an unfavorable change caused by the lack of thyroid hormones was an increase in the caspase-1 level, which was not reversed by venlafaxine alone. The results indicated that the combined administration of drugs was more effective in normalizing glycolysis and the transition to the Krebs cycle than the use of venlafaxine or L-thyroxine alone.
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spelling pubmed-82275392021-06-26 Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and Hypothyroidism Głombik, Katarzyna Detka, Jan Budziszewska, Bogusława Cells Article The clinical effectiveness of supportive therapy with thyroid hormones in drug-resistant depression is well-known; however, the mechanisms of action of these hormones in the adult brain have not been fully elucidated to date. We determined the effects of venlafaxine and/or L-thyroxine on metabolic parameters and markers involved in the regulation of synaptic plasticity and cell damage in an animal model of coexisting depression and hypothyroidism, namely, Wistar Kyoto rats treated with propylthiouracil. In this model, in relation to the depression model itself, the glycolysis process in the brain was weakened, and a reduction in pyruvate dehydrogenase in the frontal cortex was normalized only by the combined treatment with L-thyroxine and venlafaxine, whereas changes in pyruvate and lactate levels were affected by all applied therapies. None of the drugs improved the decrease in the expression of mitochondrial respiratory chain enzymes. No intensification of glucocorticoid action was shown, while an unfavorable change caused by the lack of thyroid hormones was an increase in the caspase-1 level, which was not reversed by venlafaxine alone. The results indicated that the combined administration of drugs was more effective in normalizing glycolysis and the transition to the Krebs cycle than the use of venlafaxine or L-thyroxine alone. MDPI 2021-06-05 /pmc/articles/PMC8227539/ /pubmed/34198731 http://dx.doi.org/10.3390/cells10061394 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Głombik, Katarzyna
Detka, Jan
Budziszewska, Bogusława
Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and Hypothyroidism
title Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and Hypothyroidism
title_full Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and Hypothyroidism
title_fullStr Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and Hypothyroidism
title_full_unstemmed Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and Hypothyroidism
title_short Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and Hypothyroidism
title_sort venlafaxine and l-thyroxine treatment combination: impact on metabolic and synaptic plasticity changes in an animal model of coexisting depression and hypothyroidism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227539/
https://www.ncbi.nlm.nih.gov/pubmed/34198731
http://dx.doi.org/10.3390/cells10061394
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AT budziszewskabogusława venlafaxineandlthyroxinetreatmentcombinationimpactonmetabolicandsynapticplasticitychangesinananimalmodelofcoexistingdepressionandhypothyroidism