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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Main Authors: Katarzyna Głombik, Jan Detka, Bogusława Budziszewska
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/10/6/1394
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author Katarzyna Głombik
Jan Detka
Bogusława Budziszewska
author_facet Katarzyna Głombik
Jan Detka
Bogusława Budziszewska
author_sort Katarzyna Głombik
collection DOAJ
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 doaj.art-42670779ea214b159b88d0cd70530abd2023-11-21T22:54:11ZengMDPI AGCells2073-44092021-06-01106139410.3390/cells10061394Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and HypothyroidismKatarzyna Głombik0Jan Detka1Bogusława Budziszewska2Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, PolandLaboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, PolandLaboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, PolandThe 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.https://www.mdpi.com/2073-4409/10/6/1394depressionhypothyroidismanimal disease modelslevothyroxinevenlafaxineglycolysis
spellingShingle Katarzyna Głombik
Jan Detka
Bogusława Budziszewska
Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and Hypothyroidism
Cells
depression
hypothyroidism
animal disease models
levothyroxine
venlafaxine
glycolysis
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 depression
hypothyroidism
animal disease models
levothyroxine
venlafaxine
glycolysis
url https://www.mdpi.com/2073-4409/10/6/1394
work_keys_str_mv AT katarzynagłombik venlafaxineandlthyroxinetreatmentcombinationimpactonmetabolicandsynapticplasticitychangesinananimalmodelofcoexistingdepressionandhypothyroidism
AT jandetka venlafaxineandlthyroxinetreatmentcombinationimpactonmetabolicandsynapticplasticitychangesinananimalmodelofcoexistingdepressionandhypothyroidism
AT bogusławabudziszewska venlafaxineandlthyroxinetreatmentcombinationimpactonmetabolicandsynapticplasticitychangesinananimalmodelofcoexistingdepressionandhypothyroidism