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Aurich, S.

Publications and source records attributed to Aurich, S..

2 recordsLinked to original sources

Selective octopaminergic tuning of mushroom body circuits during memory formation

The catecholamines octopamine and tyramine undoubtedly have a major impact on the life of an insect. A wide range of physiological processes and behaviours are regulated by these neurotransmitters/hormones. Octopamine and tyramine act homologous to the adrenergic system of vertebrates, primarily adapting the organism to the given situation, by switching between the states of alertness and rest. Interestingly, higher brain functions like learning and memory are also regulated by octopamine and tyramine. About 30 years ago, initial work in Drosophila has demonstrated that dopaminergic neurons signal punishment, while octopaminergic neurons signal reward during olfactory associative learning and memory. In the meantime, however, it has become clear that distinct types of dopaminergic neurons convey both reward and punishment signals to the mushroom bodies, a central brain region responsible for the formation and storage of associative memories. Although some conflicting data remain, these findings challenge the previously established model of functional segregation and may limit the proposed role of octopamine neurons as teaching neurons during memory formation. We have therefore re-examined the role of octopamine in learning and memory in Drosophila larvae. Through a combination of Ca2+ imaging, anatomical studies and gain-of-function and loss-of-function behavioural approaches, we demonstrate that octopamine signalling plays a crucial role in larval learning by modulating dopaminergic neurons across distinct cell clusters to orchestrate memory processes.

neuroscience↗

Secretin receptor as a target in gastrointestinal cancer: expression analysis and ligand development

Secretin was originally discovered as a gastrointestinal peptide that stimulates fluid secretion from pancreas and liver and delays gastric emptying. In disease, secretin receptor (SCTR) was found to occur as a splice variant in gastrinoma and pancreatic adenocarcinoma. Overexpression of SCTR has been described for gastrinomas, carcinoid tumors of the lung and cholangiocarcinoma. SCTR therefore remains a candidate target for molecular tumor imaging as well as for peptide receptor radioligand therapy (PRRT) in a number of oncological indications. The aim of this study was to characterize SCTR expression in esophageal and pancreatic cancer. 65 of 70 PDAC tissues stained strongly positive for SCTR in immunohistochemistry, as were most of 151 esophageal cancer samples, with minor influence of grading in both entities. In addition, the aim of this study was to further delineate residues in human secretin that are critical for binding to and activation of the human SCTR. For a potential development of short and metabolically stable analogs for clinical use, it was intended to probe the peptide for its capacity to incorporate deletions and substitutions without losing its affinity to SCTR. A library of 146 secretin variants containing single amino acid substitutions as well as truncations on either end was tested using {beta}-arrestin2-GFP translocation and fluorescent ligand internalization high-content analysis and cAMP assays run in agonist and antagonist mode as well as a radioligand binding. The main structural determinants of SCTR binding and activation were localized to the N-terminus, with His1, Asp3 being among the most sensitive positions, followed by Phe6, Thr7 and Leu10. Aminoterminal truncation caused a rapid decline in receptor activity and most of these variants proved to be partial agonists showing antagonistic properties. In this study, the most potent antagonist showed an IC50 of 309 {+/-} 74 nM in the {beta}-arrestin2-GFP translocation assay on human SCTR while remaining a weak partial agonist. Future studies will have to demonstrate the utility of further enhanced secretin analogues as tracers for in vivo imaging and therapy.

cancer biology↗