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Aleksandra Szopa, Urszula Doboszewska, Mariola Herbet, Sylwia Wośko, Elżbieta Wyska, Katarzyna Świąder, Anna Serefko, Agnieszka Korga, Aleksandra Wlaź, Andrzej Wróbel, Marta Ostrowska, Joanna Terlecka, Adam Kanadys, Ewa Poleszak, Jarosław Dudka, Piotr Wlaź
Recent preclinical and clinical data suggest that low dose of caffeine enhances the effects of common antidepressants. Here we investigated the effects of chronic administration of caffeine (5mg/kg, twice daily for 14days) and its withdrawal on day 15th on the activity of per se ineffective doses of fluoxetine (5mg/kg) and escitalopram (2mg/kg) given on day 15th. We found decreased immobility time in the forced swim and tail suspension tests in mice in which caffeine was administered simultaneously with antidepressants on day 15th following a 14-day caffeine treatment and no alterations in the spontaneous locomotor activity...
December 15, 2017: Toxicology and Applied Pharmacology
Lijuan Wang, Zhifen Liu, Xiaohua Cao, Jianying Li, Aixia Zhang, Ning Sun, Chunxia Yang, Kerang Zhang
AIMS: The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). However, the mechanism underlying the effects of how the SLC6A15 gene affects functional brain activity of patients with MDD remains unknown. METHODS: In the present study, we investigated the effect of the SLC6A15 gene polymorphism, rs1545843, on resting-state brain function in MDD with the imaging genomic technology and the regional homogeneity (ReHo) method...
September 2017: Genetic Testing and Molecular Biomarkers
Trillitye Paullin, Chase Powell, Christopher Menzie, Robert Hill, Feng Cheng, Christopher J Martyniuk, Sandy D Westerheide
Ovarian cancer is the most lethal gynecological cancer, with over 200,000 women diagnosed each year and over half of those cases leading to death. These poor statistics are related to a lack of early symptoms and inadequate screening techniques. This results in the cancer going undetected until later stages when the tumor has metastasized through a process that requires the epithelial to mesenchymal transition (EMT). In lieu of traditional monolayer cell culture, EMT and cancer progression in general is best characterized through the use of 3D spheroid models...
2017: PloS One
Ramesh Chandra, T Chase Francis, Hyungwoo Nam, Lace M Riggs, Michel Engeln, Sarah Rudzinskas, Prasad Konkalmatt, Scott J Russo, Gustavo Turecki, Sergio D Iniguez, Mary Kay Lobo
Previous research demonstrates that Slc6a15, a neutral amino acid transporter, is associated with depression susceptibility. However, no study examined Slc6a15 in the ventral striatum [nucleus accumbens (NAc)] in depression. Given our previous characterization of Slc6a15 as a striatal dopamine receptor 2 (D2)-neuron-enriched gene, we examined the role of Slc6a15 in NAc D2-neurons in mediating susceptibility to stress in male mice. First, we showed that Slc6a15 mRNA was reduced in NAc of mice susceptible to chronic social defeat stress (CSDS), a paradigm that produces behavioral and molecular adaptations that resemble clinical depression...
July 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jinhua Zheng, Xinglong Yang, Quanzhen Zhao, Sijia Tian, Hongyan Huang, Yalan Chen, Yanming Xu
OBJECTIVE: To investigate possible associations of Parkinson's disease (PD) with polymorphism in depression-related genes and in the alpha-synuclein (SNCA) gene. METHODS: A consecutive series of patients with PD were divided into those with depression and those without it. Patients (330) were genotyped at four single-nucleotide polymorphisms (SNPs) in four genes previously associated with depression, as well as four SNPs in the PD-associated SNCA gene. RESULTS: Of 330 patients, 125 (37...
April 15, 2017: Journal of the Neurological Sciences
Sunyoung Choi, Kyu-Man Han, June Kang, Eunsoo Won, Hun Soo Chang, Woo Suk Tae, Kyu Ri Son, Su-Jin Kim, Min-Soo Lee, Byung-Joo Ham
BACKGROUND: The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). It is presumed to be involved in the pathophysiology of MDD through regulation of glutamate transmission in the brain. However, the involvement of this gene in microstructural changes in white matter (WM) tracts remains unclear. We aimed to investigate the influence of a polymorphism of this gene (rs1545853) on the structural integrity of WM tracts in the cortico-limbic network...
2016: PloS One
Gaia De Sanctis, Michela Spinelli, Marco Vanoni, Elena Sacco
BACKGROUND: Cancer cells have an increased demand for amino acids and require transport even of non-essential amino acids to support their increased proliferation rate. Besides their major role as protein synthesis precursors, the two proteinogenic sulfur-containing amino acids, methionine and cysteine, play specific biological functions. In humans, methionine is essential for cell growth and development and may act as a precursor for cysteine synthesis. Cysteine is a precursor for the biosynthesis of glutathione, the major scavenger for reactive oxygen species...
2016: PloS One
S Santarelli, K V Wagner, C Labermaier, A Uribe, C Dournes, G Balsevich, J Hartmann, M Masana, F Holsboer, A Chen, M B Müller, M V Schmidt
Major depression is a multifactorial disease, involving both environmental and genetic risk factors. Recently, SLC6A15 - a neutral amino acid transporter mainly expressed in neurons - was proposed as a new candidate gene for major depression and stress vulnerability. Risk allele carriers for a single nucleotide polymorphism (SNP) in a SLC6A15 regulatory region display altered hippocampal volume, glutamate levels, and hypothalamus-pituitary-adrenal axis activity, all markers associated with major depression...
2016: Stress: the International Journal on the Biology of Stress
Ingo Marenholz, Jorge Esparza-Gordillo, Franz Rüschendorf, Anja Bauerfeind, David P Strachan, Ben D Spycher, Hansjörg Baurecht, Patricia Margaritte-Jeannin, Annika Sääf, Marjan Kerkhof, Markus Ege, Svetlana Baltic, Melanie C Matheson, Jin Li, Sven Michel, Wei Q Ang, Wendy McArdle, Andreas Arnold, Georg Homuth, Florence Demenais, Emmanuelle Bouzigon, Cilla Söderhäll, Göran Pershagen, Johan C de Jongste, Dirkje S Postma, Charlotte Braun-Fahrländer, Elisabeth Horak, Ludmila M Ogorodova, Valery P Puzyrev, Elena Yu Bragina, Thomas J Hudson, Charles Morin, David L Duffy, Guy B Marks, Colin F Robertson, Grant W Montgomery, Bill Musk, Philip J Thompson, Nicholas G Martin, Alan James, Patrick Sleiman, Elina Toskala, Elke Rodriguez, Regina Fölster-Holst, Andre Franke, Wolfgang Lieb, Christian Gieger, Andrea Heinzmann, Ernst Rietschel, Thomas Keil, Sven Cichon, Markus M Nöthen, Craig E Pennell, Peter D Sly, Carsten O Schmidt, Anja Matanovic, Valentin Schneider, Matthias Heinig, Norbert Hübner, Patrick G Holt, Susanne Lau, Michael Kabesch, Stefan Weidinger, Hakon Hakonarson, Manuel A R Ferreira, Catherine Laprise, Maxim B Freidin, Jon Genuneit, Gerard H Koppelman, Erik Melén, Marie-Hélène Dizier, A John Henderson, Young Ae Lee
Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12...
November 6, 2015: Nature Communications
Sara Santarelli, Christian Namendorf, Elmira Anderzhanova, Tamara Gerlach, Benedikt Bedenk, Sebastian Kaltwasser, Klaus Wagner, Christiana Labermaier, Judith Reichel, Jana Drgonova, Michael Czisch, Manfred Uhr, Mathias V Schmidt
Although mental disorders as major depression are highly prevalent worldwide their underlying causes remain elusive. Despite the high heritability of depression and a clear genetic contribution to the disease, the identification of genetic risk factors for depression has been very difficult. The first published candidate to reach genome-wide significance in depression was SLC6A15, a neuronal amino acid transporter. With a reported 1,42 fold increased risk of suffering from depression associated with a single nucleotide polymorphism (SNP) in a regulatory region of SLC6A15, the polymorphism was also found to affect hippocampal morphology, integrity, and hippocampus-dependent memory...
September 2015: Journal of Psychiatric Research
Serena Cuboni, Christian Devigny, Bastiaan Hoogeland, Andrea Strasser, Sebastian Pomplun, Barbara Hauger, Georg Höfner, Klaus T Wanner, Matthias Eder, Armin Buschauer, Florian Holsboer, Felix Hausch
B(0)AT2, encoded by the SLC6A15 gene, is a transporter for neutral amino acids that has recently been implicated in mood and metabolic disorders. It is predominantly expressed in the brain, but little is otherwise known about its function. To identify inhibitors for this transporter, we screened a library of 3133 different bioactive compounds. Loratadine, a clinically used histamine H1 receptor antagonist, was identified as a selective inhibitor of B(0)AT2 with an IC50 of 4 μM while being less active or inactive against several other members of the SLC6 family...
November 26, 2014: Journal of Medicinal Chemistry
Radosław Januchowski, Piotr Zawierucha, Marcin Ruciński, Małgorzata Andrzejewska, Karolina Wojtowicz, Michał Nowicki, Maciej Zabel
Ovarian cancer is characterized by the higher mortality among gynecological cancers. In results of MDR development during chemotherapy cancer cells become resistant to further treatment. Microarray techniques can provide information about MDR development at gene expression level. ABC and SLC transporters are most important proteins responsible for this phenomenon. In this study changes of ABC and SLC genes expression pattern in drugs resistant sublines of the A2780 ovarian cancer cell line were demonstrated...
May 2014: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jingzi Wang, Xiaobei Mao, Youwei Zhang, Lijun Xue, Xiaobei Liu, Jian Geng, Lili Ren, Hongju Yu, Longbang Chen, Xiaoyuan Chu
OBJECTIVE: To study the methylation changes in promoter CpG islands induced by low-dose X-ray radiation (LDR). METHODS: Twenty male BALB/c mice were randomly divided into control and fractionated radiation group exposed to 6 MV X-ray for 10 days (0.05 Gy/day). All the mice were sacrificed 2 h after the last radiation on day 10, and blood samples were collected for detecting DNA methylation changes using Roche-NimbleGen mouse DNA methylation 3×720K Promoter Plus CpG Island Array...
February 2014: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Susan M Mitchell, Jason P Ross, Horace R Drew, Thu Ho, Glenn S Brown, Neil F W Saunders, Konsta R Duesing, Michael J Buckley, Rob Dunne, Iain Beetson, Keith N Rand, Aidan McEvoy, Melissa L Thomas, Rohan T Baker, David A Wattchow, Graeme P Young, Trevor J Lockett, Susanne K Pedersen, Lawrence C Lapointe, Peter L Molloy
BACKGROUND: The development of colorectal cancer (CRC) is accompanied by extensive epigenetic changes, including frequent regional hypermethylation particularly of gene promoter regions. Specific genes, including SEPT9, VIM1 and TMEFF2 become methylated in a high fraction of cancers and diagnostic assays for detection of cancer-derived methylated DNA sequences in blood and/or fecal samples are being developed. There is considerable potential for the development of new DNA methylation biomarkers or panels to improve the sensitivity and specificity of current cancer detection tests...
2014: BMC Cancer
Jana Drgonova, Josefin A Jacobsson, Joan C Han, Jack A Yanovski, Robert Fredriksson, Claude Marcus, Helgi B Schiöth, George R Uhl
Brain pathways, including those in hypothalamus and nucleus of the solitary tract, influence food intake, nutrient preferences, metabolism and development of obesity in ways that often differ between males and females. Branched chain amino acids, including leucine, can suppress food intake, alter metabolism and change vulnerability to obesity. The SLC6A15 (v7-3) gene encodes a sodium-dependent transporter of leucine and other branched chain amino acids that is expressed by neurons in hypothalamus and nucleus of the solitary tract...
2013: PloS One
Carina Quast, Serena Cuboni, Daniel Bader, André Altmann, Peter Weber, Janine Arloth, Simone Röh, Tanja Brückl, Marcus Ising, Anna Kopczak, Angelika Erhardt, Felix Hausch, Susanne Lucae, Elisabeth B Binder
SLC6A15 is a neuron-specific neutral amino acid transporter that belongs to the solute carrier 6 gene family. This gene family is responsible for presynaptic re-uptake of the majority of neurotransmitters. Convergent data from human studies, animal models and pharmacological investigations suggest a possible role of SLC6A15 in major depressive disorder. In this work, we explored potential functional variants in this gene that could influence the activity of the amino acid transporter and thus downstream neuronal function and possibly the risk for stress-related psychiatric disorders...
2013: PloS One
Maria G A Hägglund, Sahar Roshanbin, Erik Löfqvist, Sofie V Hellsten, Victor C O Nilsson, Aniruddha Todkar, Yinan Zhu, Olga Stephansson, Jana Drgonova, George R Uhl, Helgi B Schiöth, Robert Fredriksson
The B(0)AT2 protein is a product of the SLC6A15 gene belonging to the SLC6 subfamily and has been shown to be a transporter of essential branched-chain amino acids. We aimed to further characterize the B(0)AT2 transporter in CNS, and to use Slc6a15 knock out (KO) mice to investigate whether B(0)AT2 is important for mediating the anorexigenic effect of leucine. We used the Slc6a15 KO mice to investigate the role of B(0)AT2 in brain in response to leucine and in particular the effect on food intake. Slc6a15 KO mice show lower reduction of food intake as well as lower neuronal activation in the ventromedial hypothalamic nucleus (VMH) in response to leucine injections compared to wild type mice...
2013: PloS One
Anna Schuhmacher, Leonhard Lennertz, Michael Wagner, Susanne Höfels, Ute Pfeiffer, Vera Guttenthaler, Wolfgang Maier, Astrid Zobel, Rainald Mössner
Major depressive disorder (MDD) is accompanied by both cognitive impairments and a hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA) system, resulting in an enhanced glucocorticoid secretion. Cortisol acts via mineralocorticoid and glucocorticoid receptors densely located in the hippocampus, a brain area that is important regarding cognitive functions and especially memory functions. Recently, a variant (rs1545843) affecting transcription of the human SLC6A15 gene has been associated with depression in a genome-wide association study...
February 2013: International Journal of Neuropsychopharmacology
Martin A Kohli, Susanne Lucae, Philipp G Saemann, Mathias V Schmidt, Ayse Demirkan, Karin Hek, Darina Czamara, Michael Alexander, Daria Salyakina, Stephan Ripke, David Hoehn, Michael Specht, Andreas Menke, Johannes Hennings, Angela Heck, Christiane Wolf, Marcus Ising, Stefan Schreiber, Michael Czisch, Marianne B Müller, Manfred Uhr, Thomas Bettecken, Albert Becker, Johannes Schramm, Marcella Rietschel, Wolfgang Maier, Bekh Bradley, Kerry J Ressler, Markus M Nöthen, Sven Cichon, Ian W Craig, Gerome Breen, Cathryn M Lewis, Albert Hofman, Henning Tiemeier, Cornelia M van Duijn, Florian Holsboer, Bertram Müller-Myhsok, Elisabeth B Binder
Major depression (MD) is one of the most prevalent psychiatric disorders and a leading cause of loss in work productivity. A combination of genetic and environmental risk factors probably contributes to MD. We present data from a genome-wide association study revealing a neuron-specific neutral amino acid transporter (SLC6A15) as a susceptibility gene for MD. Risk allele carrier status in humans and chronic stress in mice were associated with a downregulation of the expression of this gene in the hippocampus, a brain region implicated in the pathophysiology of MD...
April 28, 2011: Neuron
Young-Ho Kim, Han Cheol Lee, Seon-Young Kim, Young Il Yeom, Kyung Ju Ryu, Byung-Hoon Min, Duk-Hwan Kim, Hee Jung Son, Poong-Lyul Rhee, Jae J Kim, Jong Chul Rhee, Hee Cheol Kim, Ho-Kyung Chun, William M Grady, Yong Sung Kim
BACKGROUND: Determination of the profile of genes that are commonly methylated aberrantly in colorectal cancer (CRC) will have substantial value for diagnostic and therapeutic applications. However, there is limited knowledge of the DNA methylation pattern in CRC. MATERIALS AND METHODS: We analyzed the methylation profile of 27,578 CpG sites spanning more than 14,000 genes in CRC and in the adjacent normal mucosa with bead-chip array-based technology. RESULTS: We identified 621 CpG sites located in promoter regions and CpG islands that were greatly hypermethylated in CRC compared to normal mucosa...
August 2011: Annals of Surgical Oncology
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