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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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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]
Número total de Autores: 11
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: European Neuropsychopharmacology; v. 25, n. 4, p. 468-473, APR 2015.
Citações Web of Science: 21
Resumo

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)

Processo FAPESP: 09/14891-9 - Avaliação longitudinal dos efeitos neuroprotetores e neurotróficos induzidos pelo lítio no transtorno bipolar: identificação de alvos clinicamente relevantes
Beneficiário:Rodrigo Machado-Vieira
Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores