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

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 AKT1 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.

• Authors: Rodrigo Machado-Vieira, Marcus V Zanetti, Antonio L Teixeira, Miyuki Uno, Leandro L Valiengo, Marcio G Soeiro-de-Souza, Sueli M Oba-Shinjo, Rafael T de Sousa, Carlos A Zarate Jr, Wagner F Gattaz, Suely K N Marie
• Journal: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology (Eur Neuropsychopharmacol) Vol. 25 Issue 4 Pg. 468-73 (Apr 2015) ISSN: 1873-7862 [Electronic] Netherlands
• PMID: 25726893 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published by Elsevier B.V.

Chemical References

• Antimanic Agents
• BAD protein, human
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger
• bcl-Associated Death Protein
• NADH Dehydrogenase
• MTOR protein, human
• AKT1 protein, human
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• Lithium Chloride

Topics

• Adolescent
• Adult
• Antimanic Agents (therapeutic use)
• Bipolar Disorder (drug therapy, metabolism)
• Female
• Gene Expression Regulation (drug effects)
• Gene Regulatory Networks (drug effects, genetics)
• Humans
• Lithium Chloride (therapeutic use)
• Male
• Middle Aged
• NADH Dehydrogenase (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• RNA, Messenger (genetics)
• Signal Transduction (drug effects)
• Statistics, Nonparametric
• TOR Serine-Threonine Kinases (genetics, metabolism)
• Young Adult
• bcl-Associated Death Protein (genetics, metabolism)