TY - JOUR A1 - Schumacher, Fabian A1 - Chakraborty, Sudipta A1 - Kleuser, Burkhard A1 - Gulbins, Erich A1 - Schwerdtle, Tanja A1 - Aschner, Michael A. A1 - Bornhorst, Julia T1 - Highly sensitive isotope-dilution liquid-chromatography-electrospray ionization-tandem-mass spectrometry approach to study the drug-mediated modulation of dopamine and serotonin levels in Caenorhabditis elegans JF - Talanta : the international journal of pure and applied analytical chemistry N2 - Dopamine (DA) and serotonin (SRT) are monoamine neurotransmitters that play a key role in regulating the central and peripheral nervous system. Their impaired metabolism has been implicated in several neurological disorders, such as Parkinson's disease and depression. Consequently, it is imperative to monitor changes in levels of these low-abundant neurotransmitters and their role in mediating disease. For the first time, a rapid, specific and sensitive isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of DA and SRT in the nematode Caenorhabditis elegans (C. elegans). This model organism offers a unique approach for studying the effect of various drugs and environmental conditions on neurotransmitter levels, given by the conserved DA and SRT biology, including synaptic release, trafficking and formation. We introduce a novel sample preparation protocol incorporating the usage of sodium thiosulfate in perchloric acid as extraction medium that assures high recovery of the relatively unstable neurotransmitters monitored. Moreover, the use of both deuterated internal standards and the multiple reaction monitoring (MRM) technique allows for unequivocal quantification. Thereby, to the best of our knowledge, we achieve a detection sensitivity that clearly exceeds those of published DA and SRT quantification methods in various matrices. We are the first to show that exposure of C elegans to the monoamine oxidase B (MAOB) inhibitor selegiline or the catechol-O-methyltransferase (COMT) inhibitor tolcapone, in order to block DA and SRT degradation, resulted in accumulation of the respective neurotransmitter. Assessment of a behavioral output of the dopaminergic system (basal slowing response) corroborated the analytical LC-MS/MS data. Thus, utilization of the C elegans model system in conjunction with our analytical method is well-suited to investigate drug-mediated modulation of the DA and SRT system in order to identify compounds with neuroprotective or regenerative properties. (C) 2015 Elsevier B.V. All rights reserved. KW - Caenorhabditis elegans KW - Dopamine KW - Serotonin KW - Liquid chromatography-tandem mass spectrometry KW - Isotope-dilution analysis Y1 - 2015 U6 - https://doi.org/10.1016/j.talanta.2015.05.057 SN - 0039-9140 SN - 1873-3573 VL - 144 SP - 71 EP - 79 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - French, Alice S. A1 - Simcock, Kerry L. A1 - Rolke, Daniel A1 - Gartside, Sarah E. A1 - Blenau, Wolfgang A1 - Wright, Geraldine A. T1 - The role of serotonin in feeding and gut contractions in the honeybee JF - Journal of insect physiology KW - Honeybee KW - Apis mellifera KW - Serotonin KW - 5-HT KW - 5-HT receptor KW - Gut contractions Y1 - 2014 U6 - https://doi.org/10.1016/j.jinsphys.2013.12.005 SN - 0022-1910 SN - 1879-1611 VL - 61 SP - 8 EP - 15 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Blenau, Wolfgang A1 - Thamm, Markus T1 - Distribution of serotonin (5-HT) and its receptors in the insect brain with focus on the mushroom bodies lessons from Drosophila melanogaster and Apis mellifera JF - Arthropod structure & development N2 - The biogenic amine serotonin (5-hydroxytryptamine, 5-HT) plays a key role in regulating and modulating various physiological and behavioral processes in both protostomes and deuterostomes. The specific functions of serotonin are mediated by its binding to and subsequent activation of membrane receptors. The vast majority of these receptors belong to the superfamily of G-protein-coupled receptors. We report here the in vivo expression pattern of a recently characterized 5-HT(1) receptor of the honeybee Apis mellifera (Am5-HT(1A)) in the mushroom bodies. In addition, we summarize current knowledge on the distribution of serotonin and serotonin receptor subtypes in the brain and specifically in the mushroom bodies of the fruit fly Drosophila melanogaster and the honeybee. Functional studies in these two species have shown that serotonergic signaling participates in various behaviors including aggression, sleep, circadian rhythms, responses to visual stimuli, and associative learning. The molecular, pharmacological, and functional properties of identified 5-HT receptor subtypes from A. mellifera and D. melanogaster will also be summarized in this review. KW - Apis mellifera KW - G-protein-coupled receptor KW - Drosophila melanogaster KW - Mushroom body KW - Serotonin Y1 - 2011 U6 - https://doi.org/10.1016/j.asd.2011.01.004 SN - 1467-8039 VL - 40 IS - 5 SP - 381 EP - 394 PB - Elsevier CY - Oxford ER -