The Interaction of TRAF6 With Neuroplastin Promotes Spinogenesis During Early Neuronal Development

Creators: Vemula, Sampath Kumar; Malci, Ayse; Junge, Lennart; Lehmann, Anne-Christin; Rama, Ramya; Hradsky, Johannes; Matute, Ricardo A.; Weber, André; Prigge, Matthias; Naumann, Michael; Kreutz, Michael R.; Seidenbecher, Constanze I.; Gundelfinger, Eckart D.; Herrera-Molina, Rodrigo

Abstract

Chagas disease (CD) is a tropical and still neglected disease caused by Trypanosoma cruzi that affects >8 million of people worldwide. Although limited, emerging data suggest that gut microbiota dysfunction may be a new mechanism underlying CD pathogenesis. T. cruzi infection leads to changes in the gut microbiota composition of vector insects, mice, and humans. Alterations in insect and mice microbiota due to T. cruzi have been associated with a decreased immune response against the parasite, influencing the establishment and progression of infection. Further, changes in the gut microbiota are linked with inflammatory and neuropsychiatric disorders, comorbid conditions in CD. Therefore, this review article critically analyses the current data on CD and the gut microbiota of insects, mice, and humans and discusses its importance for CD pathogenesis. An enhanced understanding of host microbiota will be critical for the development of alternative therapeutic approaches to target CD, such as gut microbiota-directed interventions.

Additional Information

© 2020 Vemula, Malci, Junge, Lehmann, Rama, Hradsky, Matute, Weber, Prigge, Naumann, Kreutz, Seidenbecher, Gundelfinger and Herrera-Molina. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Received: 02 July 2020; Accepted: 11 November 2020; Published: 09 December 2020. We thank to Kathrin Pohlmann for her technical work and Dirk Montag for providing neuroplastin mice. Preliminary manuscript has been released as a pre-print at bioRxiv (Vemula et al., 2020). This study was supported by funding from the DFG GRK 1167 and the ABINEP graduate school funded by the federal state of Saxony-Anhalt and the European Structural and Investment Funds (ESF, 2014-2020), project number ZS/2016/08/80645 to EG, MN, and CS. RM received funding from FONDECYT Grant No. 1181260. MP was supported by the Leibniz Association (SheLi J28/2017). RH-M is an LSA fellow from the Center for Behavioral Brain Sciences (CBBS) and received the DAAD grant no. 57514679. EG was supported by the DFG SFB 854, and CS and EG received funding from BMBF 01DN17002. Author Contributions. SV and AM conducted most of the experiments and raw data analysis. LJ conducted the PMCA experiments. A-CL and RR made and characterized constructs. JH conducted the SPR experiments. RM conducted the in silico modeling. MP conducted the Patch Clamp experiments. RH-M supported the experiments, conducted the MEA and Patch Clamp experiments, and wrote the manuscript draft. RH-M, MK, MP, MN, CS, and EG contributed to the experimental design and data interpretation. All the authors contributed to the manuscript's final version. Data Availability Statement. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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