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Mitochondrial Alterations in Fibroblasts of Early Stage Bipolar Disorder Patients

dc.contributor.authorMarques, AP
dc.contributor.authorResende, R
dc.contributor.authorSilva, DF
dc.contributor.authorBatista, M
dc.contributor.authorPereira, D
dc.contributor.authorWildenberg, B
dc.contributor.authorMorais, S
dc.contributor.authorMacedo, A
dc.contributor.authorPais, C
dc.contributor.authorMelo, JB
dc.contributor.authorMadeira, N
dc.contributor.authorPereira, CF
dc.date.accessioned2021-08-31T10:40:15Z
dc.date.available2021-08-31T10:40:15Z
dc.date.issued2021
dc.description.abstractThis study aims to evaluate whether mitochondrial changes occur in the early stages of bipolar disorder (BD). Using fibroblasts derived from BD patients and matched controls, the levels of proteins involved in mitochondrial biogenesis and dynamics (fission and fusion) were evaluated by Western Blot analysis. Mitochondrial membrane potential (MMP) was studied using the fluorescent probe TMRE. Mitochondrial morphology was analyzed with the probe Mitotracker Green and mitophagy was evaluated by quantifying the co-localization of HSP60 (mitochondria marker) and LC3B (autophagosome marker) by immunofluorescence. Furthermore, the activity of the mitochondrial respiratory chain and the glycolytic capacity of controls and BD patients-derived cells were also studied using the Seahorse technology. BD patient-derived fibroblasts exhibit fragmented mitochondria concomitantly with changes in mitochondrial dynamics and biogenesis in comparison with controls. Moreover, a decrease in the MMP and increased mitophagy was observed in fibroblasts obtained from BD patients when compared with control cells. Impaired energetic metabolism due to inhibition of the mitochondrial electron transport chain (ETC) and subsequent ATP depletion, associated with glycolysis stimulation, was also a feature of BD fibroblasts. Overall, these results support the fact that mitochondrial disturbance is an early event implicated in BD pathophysiology that might trigger neuronal changes and modification of brain circuitry.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBiomedicines. 2021 May 7;9(5):522.pt_PT
dc.identifier.doi10.3390/biomedicines9050522pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.4/2326
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectMitocondriapt_PT
dc.subjectPerturbação Bipolarpt_PT
dc.titleMitochondrial Alterations in Fibroblasts of Early Stage Bipolar Disorder Patientspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue5pt_PT
oaire.citation.startPage522pt_PT
oaire.citation.titleBiomedicinespt_PT
oaire.citation.volume9pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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