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proteome, antidepressant

Chao Chen, Yuan Hu, Xian-Zhe Dong, Xiao-Jiang Zhou, Li-Hua Mu, Ping Liu
Shen-Zhi-Ling (SZL) is a Chinese medicine formulated from a Kai-Xin-San decoction that is commonly used to treat depression caused by dual deficiencies in the heart and spleen. However, the underlying mechanisms remain unclear. We investigated biological changes in depression patients (DPs) exhibiting antidepressant responses to SZL treatment using proteomic techniques. We performed label-free quantitative proteomic analysis and liquid chromatography-tandem mass spectrometry to discover and examine altered proteins involved in depression and antidepressant treatment...
March 21, 2018: Cellular and Molecular Neurobiology
Katarzyna Głombik, Aneta Stachowicz, Ewa Trojan, Joanna Ślusarczyk, Maciej Suski, Katarzyna Chamera, Katarzyna Kotarska, Rafał Olszanecki, Agnieszka Basta-Kaim
BACKGROUND: Alteration in the brain mitochondrial functions have been suggested to participate, as a relevant factor, in the development of mental disorders. Therefore, the brain mitochondria may be a crucial therapeutic target in the course of depression. METHODS: Our goal was to find out the impact of two antidepressant drugs with various mechanisms of action - imipramine and fluoxetine, on the frontal cortex mitochondria-enriched fraction in an animal model of depression based on the prenatal stress procedure...
November 26, 2017: Pharmacological Reports: PR
Mi Zhou, Zhao Liu, Jia Yu, Shuiming Li, Min Tang, Li Zeng, Haiyang Wang, Hong Xie, Li Peng, Haojun Huang, Chanjuan Zhou, Peng Xie, Jian Zhou
The amygdala plays a key role in the pathophysiology of depression, but the molecular mechanisms underlying amygdalar hyperactivity in depression remain unclear. In this study, we used a chronic mild stress (CMS) protocol to separate susceptible and insusceptible rat subgroups. Proteomes in the amygdalae were analyzed differentially across subgroups based on labeling with isobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry. Of 2562 quantified proteins, 102 were differentially expressed...
February 13, 2018: Neuroscience
Dong Ik Park, Jerko Štambuk, Genadij Razdorov, Maja Pučić-Baković, Daniel Martins-de-Souza, Gordan Lauc, Christoph W Turck
While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated. In our exploratory study, we analysed N-glycan profiles in blood plasma samples collected from MDD patients (n = 18) and found gender-dependent correlations with severity of depressive symptoms prior to initiating antidepressant treatment. In addition, several N-glycosylation traits showed gender-dependent associations with clinical antidepressant response...
January 9, 2018: Scientific Reports
Yuqing Zhang, Shuai Yuan, Juncai Pu, Lining Yang, Xinyu Zhou, Lanxiang Liu, Xiaofeng Jiang, Hanping Zhang, Teng Teng, Lu Tian, Peng Xie
Major depressive disorder (MDD) is a prevalent and serious mental disorder with high rates of suicide and disability. However, the underlying pathogenesis of MDD is complicated and remains largely unclear. An integrated analysis of multiple types of omics data may improve comprehensive understanding of the entire molecular mechanism of MDD. In this study, we applied an integrated analysis of gas chromatography/mass spectrometry (GC-MS)-based metabolomics and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics to investigate changes in the hippocampus in the chronic unpredictable mild stress (CUMS) rat model of depression...
February 10, 2018: Neuroscience
Katja Weckmann, Michael J Deery, Julie A Howard, Renata Feret, John M Asara, Frederik Dethloff, Michaela D Filiou, Jamie Iannace, Christiana Labermaier, Giuseppina Maccarrone, Christian Webhofer, Larysa Teplytska, Kathryn Lilley, Marianne B Müller, Christoph W Turck
Fewer than 50% of all patients with major depressive disorder (MDD) treated with currently available antidepressants (ADs) show full remission. Moreover, about one third of the patients suffering from MDD does not respond to conventional ADs and develop treatment-resistant depression (TRD). Ketamine, a non-competitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been shown to have a rapid antidepressant effect, especially in patients suffering from TRD. Hippocampi of ketamine-treated mice were analysed by metabolome and proteome profiling to delineate ketamine treatment-affected molecular pathways and biosignatures...
November 17, 2017: Scientific Reports
G Voegeli, M L Cléry-Melin, N Ramoz, P Gorwood
BACKGROUND: Antidepressant drugs are widely prescribed, but response rates after 3 months are only around one-third, explaining the importance of the search of objectively measurable markers predicting positive treatment response. These markers are being developed in different fields, with different techniques, sample sizes, costs, and efficiency. It is therefore difficult to know which ones are the most promising. OBJECTIVE: Our purpose was to compute comparable (i...
December 2017: Drugs
Azmeraw T Amare, Klaus Oliver Schubert, Bernhard T Baune
Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry...
September 2017: EPMA Journal
Vanja Dakic, Juliana Minardi Nascimento, Rafaela Costa Sartore, Renata de Moraes Maciel, Draulio B de Araujo, Sidarta Ribeiro, Daniel Martins-de-Souza, Stevens K Rehen
Dimethyltryptamines are entheogenic serotonin-like molecules present in traditional Amerindian medicine recently associated with cognitive gains, antidepressant effects, and changes in brain areas related to attention. Legal restrictions and the lack of adequate experimental models have limited the understanding of how such substances impact human brain metabolism. Here we used shotgun mass spectrometry to explore proteomic differences induced by 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) on human cerebral organoids...
October 9, 2017: Scientific Reports
Selena S Schattauer, Benjamin B Land, Kathryn L Reichard, Antony D Abraham, Lauren M Burgeno, Jamie R Kuhar, Paul E M Phillips, Shao En Ong, Charles Chavkin
Inactivation of opioid receptors limits the therapeutic efficacy of morphine-like analgesics and mediates the long duration of kappa opioid antidepressants by an uncharacterized, arrestin-independent mechanism. Here we use an iterative, discovery-based proteomic approach to show that following opioid administration, peroxiredoxin 6 (PRDX6) is recruited to the opioid receptor complex by c-Jun N-terminal kinase (JNK) phosphorylation. PRDX6 activation generates reactive oxygen species via NADPH oxidase, reducing the palmitoylation of receptor-associated Gαi in a JNK-dependent manner...
September 29, 2017: Nature Communications
Christoph W Turck, Paul C Guest, Giuseppina Maccarrone, Marcus Ising, Stefan Kloiber, Susanne Lucae, Florian Holsboer, Daniel Martins-de-Souza
The current inability of clinical psychiatry to objectively select the most appropriate treatment is a major factor contributing to the severity and clinical burden of major depressive disorder (MDD). Here, we have attempted to identify plasma protein signatures in 39 MDD patients to predict response over a 6-week treatment period with antidepressants. LC-MS/MS analysis showed that differences in the levels of 29 proteins at baseline were found in the group with a favorable treatment outcome. Most of these proteins were components of metabolism or immune response pathways as well as multiple components of the coagulation cascade...
2017: Frontiers in Molecular Neuroscience
Indira Mendez-David, Céline Boursier, Valérie Domergue, Romain Colle, Bruno Falissard, Emmanuelle Corruble, Alain M Gardier, Jean-Philippe Guilloux, Denis J David
The incorporation of peripheral biomarkers in the treatment of major depressive disorders (MDD) could improve the efficiency of treatments and increase remission rate. Peripheral blood mononuclear cells (PBMCs) represent an attractive biological substrate allowing the identification of a drug response signature. Using a proteomic approach with high-resolution mass spectrometry, the present study aimed to identify a biosignature of antidepressant response (fluoxetine, a Selective Serotonin Reuptake Inhibitor) in PBMCs in a mouse model of anxiety/depression...
2017: Frontiers in Cellular Neuroscience
Bharathi S Gadad, Manish K Jha, Andrew Czysz, Jennifer L Furman, Taryn L Mayes, Michael P Emslie, Madhukar H Trivedi
BACKGROUND: In recent years, we have accomplished a deeper understanding about the pathophysiology of major depressive disorder (MDD). Nevertheless, this improved comprehension has not translated to improved treatment outcome, as identification of specific biologic markers of disease may still be crucial to facilitate a more rapid, successful treatment. Ongoing research explores the importance of screening biomarkers using neuroimaging, neurophysiology, genomics, proteomics, and metabolomics measures...
July 5, 2017: Journal of Affective Disorders
Bharathi S Gadad, Manish K Jha, Bruce D Grannemann, Taryn L Mayes, Madhukar H Trivedi
Animal and human studies suggest an association between depression and aberrant immune response. Further, common inflammatory markers may change during the course of antidepressant treatment in patients. The objective of this study was to evaluate changes in inflammatory markers and clinical outcomes from subjects enrolled in the Combining Medications to Enhance Depression Outcome (CO-MED) trial. At baseline and week 12 (treatment completion), plasma samples of 102 participants were analyzed via a multiplex assay comprised of inflammatory markers using a 27-plex standard assay panel plus a 4-plex human acute phase xMAP technology based platform...
November 2017: Journal of Psychiatric Research
Thomas Frodl
Major depressive disorder is one of the leading causes of disability in the world since depression is highly frequent and causes a strong burden. In order to reduce the duration of depressive episodes, clinicians would need to choose the most effective therapy for each individual right away. A prerequisite for this would be to have biomarkers at hand that would predict which individual would benefit from which kind of therapy (for example, pharmacotherapy or psychotherapy) or even from which kind of antidepressant class...
2017: F1000Research
Katarzyna Głombik, Aneta Stachowicz, Ewa Trojan, Rafał Olszanecki, Joanna Ślusarczyk, Maciej Suski, Katarzyna Chamera, Bogusława Budziszewska, Władysław Lasoń, Agnieszka Basta-Kaim
Several lines of evidence indicate that adverse experience in early life may be a triggering factor for disturbances in the brain mitochondrial proteins and lead to the development of depression in adulthood. On the other hand, little is known about the impact of chronic administration of various antidepressant drugs on the brain mitochondria, as a target for the pharmacotherapy of depression. The purpose of our study was to compare the impact of chronic treatment with two antidepressant drugs with different mechanisms of action, a tricyclic antidepressant (TCA), imipramine, and an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class, fluoxetine, on the mitochondria-enriched subproteome profile in the hippocampus of 3-month-old male rats following a prenatal stress procedure (an animal model of depression)...
August 1, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
D I Park, C Dournes, I Sillaber, M Ising, J M Asara, C Webhofer, M D Filiou, M B Müller, C W Turck
The aim of this study was to identify molecular pathways related to antidepressant response. We administered paroxetine to the DBA/2J mice for 28 days. Following the treatment, the mice were grouped into responders or non-responders depending on the time they spent immobile in the forced swim test. Hippocampal metabolomics and proteomics analyses revealed that chronic paroxetine treatment affects glutamate-related metabolite and protein levels differentially in the two groups. We found significant differences in the expression of N-methyl-d-aspartate receptor and neuronal nitric oxide synthase proteins between the two groups, without any significant alterations in the respective transcript levels...
April 4, 2017: Translational Psychiatry
Uhna Sung, Francesca Binda, Valentina Savchenko, William A Owens, Lynette C Daws
The antidepressant-sensitive norepinephrine (NE) transporter (NET) inactivates NE released during central and peripheral neuronal activity by transport into presynaptic cells. Altered NE clearance due to dysfunction of NET has been associated with the development of mental illness and cardiovascular diseases. NET activity in vivo is influenced by stress, neuronal activity, hormones and drugs. We investigated the mechanisms of Ca2+ regulation of NET and found that Ca2+ influenced both Vmax and Km for NE transport into cortical synaptosomes...
October 2017: Journal of Chemical Neuroanatomy
Dong Ik Park, Carine Dournes, Inge Sillaber, Manfred Uhr, John M Asara, Nils C Gassen, Theo Rein, Marcus Ising, Christian Webhofer, Michaela D Filiou, Marianne B Müller, Christoph W Turck
Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively...
October 12, 2016: Scientific Reports
Lucia Carboni, Thanh-Phuong Nguyen, Laura Caberlotto
PURPOSE: The pathophysiological basis of major depression is incompletely understood. Recently, numerous proteomic studies have been performed in rodent models of depression to investigate the molecular underpinnings of depressive-like behaviours with an unbiased approach. The objective of the study is to integrate the results of these proteomic studies in depression models to shed light on the most relevant molecular pathways involved in the disease. EXPERIMENTAL DESIGN: Network analysis is performed integrating preexisting proteomic data from rodent models of depression...
December 2016: Proteomics. Clinical Applications
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