Openly accessible

Perturbations in the apoptotic pathway and mitochondrial network dynamics in peripheral blood mononuclear cells from bipolar disorder patients

Scaini, G., Fries, G. R., Valvassori, S. S., Zeni, C. P., Zunta-Soares, G., Berk, M., Soares, J. C. and Quevedo, J. 2017, Perturbations in the apoptotic pathway and mitochondrial network dynamics in peripheral blood mononuclear cells from bipolar disorder patients, Translational psychiatry, vol. 7, pp. 1-10, doi: 10.1038/tp.2017.83.

Attached Files
Name Description MIMEType Size Downloads
berk-perturbationsinthe-2017.pdf Published version application/pdf 1.76MB 16

Title Perturbations in the apoptotic pathway and mitochondrial network dynamics in peripheral blood mononuclear cells from bipolar disorder patients
Author(s) Scaini, G.
Fries, G. R.
Valvassori, S. S.
Zeni, C. P.
Zunta-Soares, G.
Berk, M.ORCID iD for Berk, M. orcid.org/0000-0002-5554-6946
Soares, J. C.
Quevedo, J.
Journal name Translational psychiatry
Volume number 7
Article ID e1111
Start page 1
End page 10
Total pages 10
Publisher Springer Nature
Place of publication New York, N.Y.
Publication date 2017-05
ISSN 2158-3188
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Psychiatry
INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW
DORSOLATERAL PREFRONTAL CORTEX
CYTOCHROME-C
HUMAN SURVIVIN
RATING-SCALE
DSM-IV
FISSION
FUSION
DEATH
SCHIZOPHRENIA
Summary Bipolar disorder (BD) is a severe psychiatric disorder characterized by phasic changes of mood and can be associated with progressive structural brain change and cognitive decline. The numbers and sizes of glia and neurons are reduced in several brain areas, suggesting the involvement of apoptosis in the pathophysiology of BD. Because the changes in mitochondrial dynamics are closely related with the early process of apoptosis and the specific processes of apoptosis and mitochondrial dynamics in BD have not been fully elucidated, we measured the apoptotic pathway and the expression of mitochondrial fission/fusion proteins from BD patients and healthy controls. We recruited 16 patients with BD type I and sixteen well-matched healthy controls and investigated protein levels of several pro-apoptotic and anti-apoptotic factors, as well as the expression of mitochondrial fission/fusion proteins in peripheral blood mononuclear cells (PBMCs). Our results showed that the levels of the anti-apoptotic proteins Bcl-xL, survivin and Bcl-xL/Bak dimer were significantly decreased, while active caspase-3 protein levels were significantly increased in PBMCs from BD patients. Moreover, we observed the downregulation of the mitochondrial fusion-related proteins Mfn2 and Opa1 and the upregulation of the fission protein Fis1 in PBMCs from BD patients, both in terms of gene expression and protein levels. We also showed a significantly decrease in the citrate synthase activity. Finally, we found a positive correlation between Mfn2 and Opa1 with mitochondrial content markers, as well as a negative correlation between mitochondrial fission/fusion proteins and apoptotic markers. Overall, data reported here are consistent with the working hypothesis that apoptosis may contribute to cellular dysfunction, brain volume loss and progressive cognitive in BD. Moreover, we show an important relationship between mitochondrial dynamics and the cell death pathway activation in BD patients, supporting the link between mitochondrial dysfunction and the pathophysiology of BD.
Language eng
DOI 10.1038/tp.2017.83
Field of Research 110319 Psychiatry (incl Psychotherapy)
Socio Economic Objective 920410 Mental Health
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2017, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30095891

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 3 times in TR Web of Science
Scopus Citation Count Cited 3 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 93 Abstract Views, 18 File Downloads  -  Detailed Statistics
Created: Tue, 25 Jul 2017, 15:27:38 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.