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Ketamine and proteomics

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
J Oras, B Redfors, A Ali, J Lundgren, C Sihlbom, A Thorsell, H Seeman-Lodding, E Omerovic, S-E Ricksten
BACKGROUND: Takotsubo syndrome (TS) is an acute cardiac condition with a substantial mortality for which no specific treatment is available. We have previously shown that isoflurane attenuates the development of left ventricular (LV) dysfunction in an experimental TS-model. We compared the effects of equi-anaesthetic doses of isoflurane, propofol and ketamine+midazolam on haemodynamics, global and regional LV systolic function and the activation of intracellular metabolic pathways in experimental TS...
March 2017: Acta Anaesthesiologica Scandinavica
Cristina Blaj, Agnes Bringmann, Eva Marina Schmidt, Manuela Urbischek, Sebastian Lamprecht, Thomas Fröhlich, Georg J Arnold, Stefan Krebs, Helmut Blum, Heiko Hermeking, Andreas Jung, Thomas Kirchner, David Horst
Purpose: Constitutively active WNT signaling is a hallmark of colorectal cancers and a driver of malignant tumor progression. Therapeutic targeting of WNT signaling is difficult due to high pathway complexity and its role in tissue homeostasis. Here, we identify the transcription factor ADNP as a pharmacologically inducible repressor of WNT signaling in colon cancer. Experimental Design: We used transcriptomic, proteomic, and in situ analyses to identify ADNP expression in colorectal cancer and cell biology approaches to determine its function...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hsueh-Hui Yang, Wei-Jun Zhai, Hann-Chorng Kuo
PURPOSE: Ketamine-induced cystitis (KC) among chronic ketamine young abusers has increased dramatically and it has brought attention for Urologists. The underlying pathophysiological mechanism(s) of KC is still unclear. Therefore, the purpose of this study is to elucidate the possible pathophysiological mechanism(s) of KC through proteomic techniques. EXPERIMENTAL DESIGN: Bladder tissues are obtained from seven patients with KC, seven patients with interstitial cystitis/bladder pain syndrome, and five control subjects who underwent video-urodynamic study followed by augmentation enterocystoplasty to increase bladder capacity...
March 2017: Proteomics. Clinical Applications
David A Cox, Michael G Gottschalk, Hendrik Wesseling, Agnes Ernst, Jason D Cooper, Sabine Bahn
Pharmacological and genetic rodent models of schizophrenia play an important role in the drug discovery pipeline, but quantifying the molecular similarity of such models with the underlying human pathophysiology has proved difficult. We developed a novel systems biology methodology for the direct comparison of anterior prefrontal cortex tissue from four established glutamatergic rodent models and schizophrenia patients, enabling the evaluation of which model displays the greatest similarity to schizophrenia across different pathophysiological characteristics of the disease...
November 2016: Schizophrenia Research
C-H Zhao, G-H Li, Q Wang, B Zhao, Z-B Wang
OBJECTIVE: We studied the mechanisms of protective effects of propofol on ketamine-induced damage to neonatal cognitive function. MATERIALS AND METHODS: We utilized a rat model of ketamine anaesthesia. Eighty neonatal rats (7 days after birth) were divided into four groups: normal saline group, ketamine group, and low- and high-dose propofol combined with ketamine groups. Six hours after anaesthesia, we obtained hippocampal tissue, and quantified apoptotic index and total protein concentration, and assessed global proteomics changes induced by two tested drugs...
2016: European Review for Medical and Pharmacological Sciences
Mark J Niciu, Daniel C Mathews, Dawn F Ionescu, Erica M Richards, Maura L Furey, Peixiong Yuan, Allison C Nugent, Ioline D Henter, Rodrigo Machado-Vieira, Carlos A Zarate
BACKGROUND: Recently, surrogate neurobiological biomarkers that correlate with target engagement and therapeutic response have been developed and tested in early phase studies of mood disorders. OBJECTIVE: The identification of biomarkers could help develop personalized psychiatric treatments that may impact public health. METHODS: These biomarkers, which are associated with clinical response post-treatment, can be directly validated using multimodal approaches including genetic tools, proteomics/metabolomics, peripheral measures, neuroimaging, biostatistical predictors, and clinical predictors...
2014: Revista de Psiquiatria Clínica
Kenneth A Jones, Frank S Menniti, Digavalli V Sivarao
Neuroscience has made tremendous progress delineating the cellular and molecular processes important for understanding neuronal development and behavior, but this knowledge has been slow to translate to new treatments for psychiatric illness. To accelerate this transfer of knowledge to the human condition requires the wide-scale adoption of biomarkers that can bridge preclinical and clinical discoveries, and serve as surrogate measures of efficacy before commencing expensive phase III studies. Several biomarker methodologies, including imaging, electroencephalography (EEG), and blood transcriptomics/proteomics, are now showing promise...
May 2015: Annals of the New York Academy of Sciences
Hendrik Wesseling, Hassan Rahmoune, Mark Tricklebank, Paul C Guest, Sabine Bahn
There is substantial interest in the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine in psychiatric research because it exerts acute psychotomimetic and rapid antidepressant effects in rodents and humans. Here, we investigated proteomic changes in brain and serum after acute treatment of rats with ketamine using two targeted proteomic profiling methods. Multiplex immunoassay profiling of serum identified altered levels of interleukin 4, tumor necrosis factor alpha, and fibroblast growth factor 9, suggesting a link between ketamine exposure and peripheral inflammation and growth factor dysregulation...
January 2, 2015: Journal of Proteome Research
Mark J Niciu, Daniel C Mathews, Allison C Nugent, Dawn F Ionescu, Maura L Furey, Erica M Richards, Rodrigo Machado-Vieira, Carlos A Zarate
An impediment to progress in mood disorders research is the lack of analytically valid and qualified diagnostic and treatment biomarkers. Consistent with the National Institute of Mental Health (NIMH)'s Research Domain Criteria (RDoC) initiative, the lack of diagnostic biomarkers has precluded us from moving away from a purely subjective (symptom-based) toward a more objective diagnostic system. In addition, treatment response biomarkers in mood disorders would facilitate drug development and move beyond trial-and-error toward more personalized treatments...
April 2014: Depression and Anxiety
Di Gu, Jun Huang, Zhengfei Shan, Youle Yin, Shaobin Zheng, Peng Wu
OBJECTIVES: Long-term ketamine abuse can affect the urinary system, resulting in interstitial cystitis-like syndrome. However, its pathogenesis remains unclear. In the present study, a proteomic approach of two-dimensional difference gel electrophoresis followed by matrix-assisted laser desorption/ionization time-of-light mass spectrometry was carried out to investigate the potential disease-associated proteins in a rat model of ketamine-associated cystitis. METHODS: Rats were randomly assigned to control, normal saline, low dose of ketamine (10 mg/kg) and high-dose of ketamine (50 mg/kg) groups with six rats in each group...
October 2013: International Journal of Urology: Official Journal of the Japanese Urological Association
K-H Smalla, M Mikhaylova, J Sahin, H-G Bernstein, B Bogerts, A Schmitt, R van der Schors, A B Smit, K W Li, E D Gundelfinger, M R Kreutz
Many studies in recent years suggest that schizophrenia is a synaptic disease that crucially involves a hypofunction of N-methyl-D-aspartate receptor-mediated signaling. However, at present it is unclear how these pathological processes are reflected in the protein content of the synapse. We have employed two-dimensional gel electrophoresis in conjunction with mass spectrometry to characterize and compare the synaptic proteomes of the human left dorsolateral prefrontal cortex in chronic schizophrenia and of the cerebral cortex of rats treated subchronically with ketamine...
September 2008: Molecular Psychiatry
William Slikker, Merle G Paule, Linnzi K M Wright, Tucker A Patterson, Cheng Wang
Systems biology/toxicology involves the iterative and integrative study of perturbations by chemicals and other stressors of gene and protein expression that are linked firmly to toxicological outcome. In this review, the value of systems biology to enhance the understanding of complex biological processes such as neurodegeneration in the developing brain is explored. Exposure of the developing mammal to NMDA (N-methyl-D-aspartate) receptor antagonists perturbs the endogenous NMDA receptor system and results in enhanced neuronal cell death...
May 2007: Journal of Applied Toxicology: JAT
William Slikker, Zengjun Xu, Cheng Wang
Systems biology can be applied to enhance the understanding of complex biological processes such as apoptosis in the developing brain. Systems biology, as applied to toxicology, provides a structure to arrange information in the form of a biological model. The approach allows for the subsequent and iterative perturbation of the initial model with the use of toxicants, and the comparison of the resulting data against the proposed biological model. It is postulated that the exposure of the developing rat to NMDA antagonists, e...
January 2005: Reproductive Toxicology
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