{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:17:29Z","timestamp":1788999449872,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,5]],"date-time":"2021-06-05T00:00:00Z","timestamp":1622851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2017\/25\/B\/NZ7\/01708"],"award-info":[{"award-number":["2017\/25\/B\/NZ7\/01708"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells10061394","type":"journal-article","created":{"date-parts":[[2021,6,6]],"date-time":"2021-06-06T23:59:55Z","timestamp":1623023995000},"page":"1394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and Hypothyroidism"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7695-2556","authenticated-orcid":false,"given":"Katarzyna","family":"G\u0142ombik","sequence":"first","affiliation":[{"name":"Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, Sm\u0119tna 12, 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9866-5777","authenticated-orcid":false,"given":"Jan","family":"Detka","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, Sm\u0119tna 12, 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogus\u0142awa","family":"Budziszewska","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, Sm\u0119tna 12, 31-343 Krak\u00f3w, Poland"},{"name":"Department of Biochemical Toxicology, Medical College, Jagiellonian University, Medyczna 9, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.psyneuen.2008.12.012","article-title":"The effect of antidepressant drugs on the HPA axis activity, glucocorticoid receptor level and FKBP51 concentration in prenatally stressed rats","volume":"34","author":"Budziszewska","year":"2009","journal-title":"Psychoneuroendocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0278-5846(94)00101-M","article-title":"Evidence for an immune response in major depression: A review and hypothesis","volume":"19","author":"Maes","year":"1995","journal-title":"Prog. 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