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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Decreased AKT1/mTOR pathway mRNA expression in short-term bipolar disorder

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Author(s):
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Machado-Vieira, Rodrigo [1, 2, 3] ; Zanetti, Marcus V. [1, 3] ; Teixeira, Antonio L. [4] ; Uno, Miyuki [5] ; Valiengo, Leandro L. [3] ; Soeiro-de-Souza, Marcio G. [6] ; Oba-Shinjo, Sueli M. [2] ; de Sousa, Rafael T. [3] ; Zarate, Jr., Carlos. A. [2] ; Gattaz, Wagner F. [1, 3] ; Marie, Suety K. N. [5]
Total Authors: 11
Affiliation:
[1] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-05508 Sao Paulo - Brazil
[2] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 - USA
[3] Univ Sao Paulo, Dept & Inst Psychiat, Neurosci Lab, LIM 27, BR-05508 Sao Paulo - Brazil
[4] Univ Fed Minas Gerais, Interdisciplinary Lab Med Invest, Belo Horizonte, MG - Brazil
[5] Univ Sao Paulo, Dept Neurol, Mol & Cellular Biol Lab, BR-05508 Sao Paulo - Brazil
[6] Univ Sao Paulo, Dept Psychiat, Mood Disorders Program, GRUDA, BR-05508 Sao Paulo - Brazil
Total Affiliations: 6
Document type: Journal article
Source: European Neuropsychopharmacology; v. 25, n. 4, p. 468-473, APR 2015.
Web of Science Citations: 21
Abstract

Strong evidence implicates intracellular signaling cascades dysfunction in the pathophysiology of Bipolar Disorder (BD). Regulation of AKT/mTOR pathway is a critical signaling pathway in synaptic neurotransmission and plasticity, also modulating cell proliferation and migration. Gene expression of the AKT/mTOR pathway was assessed in 25 BD (DSM-IV-TR criteria) unmedicated depressed individuals at baseline and after 6 weeks of lithium therapy and 31 matched healthy controls. Decreases in blood AKT/ and mTOR mRNA expression, as well as in BAD/BCL-2 expression ratio were observed in short-term BD patients during depressive episodes in comparison to healthy controls. There was no significant change in the expression of AKT1, mTOR, BCL-2, BAD and NDUFA6 after lithium therapy in the total group of BD subjects. However, the changes in AKT1 expression after lithium treatment were positively correlated with depression improvement. An integrated activity within this pathway was observed at both baseline and post-treatment. The present results support an integrated AKT/mTOR signaling pathway activity in a similar fashion to the described in previous human postmortem and rodents brain studies. Overall, the results reinforce a role for AKT1 and mTOR in the pathophysiology of BD and support the relevance of blood mRNA expression as a valid surrogate biological source to study brain intracellular signaling cascades changes and convergent molecular pathways in psychiatric disorders. Published by Elsevier B.V. (AU)

FAPESP's process: 09/14891-9 - Longitudinal study on the neuroprotective and neurotrophic effects of lithium in bipolar disorder: identification of cellular and molecular targets clinically relevant
Grantee:Rodrigo Machado-Vieira
Support Opportunities: Research Grants - Young Investigators Grants