Loss of TDP-43 function causes neurodegeneration in the mice brain

Abstract

Event Abstract Back to Event Loss of TDP-43 function causes neurodegeneration in the mice brain Ming-Che J. Wu1*, Lien-Szu Wu1, Wei-Cheng Cheng1 and C.-K. J. Shen1 1 Academia Sinica, Institute of Molecular Biology, Taiwan Tar-DNA binding protein 43 (TDP-43), a nuclear protein, plays an important role in regulating transcription and mRNA splicing. TDP-43 is the major constituent of proteinaceous inclusion in the cytoplasm of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) patients‚Äô diseased neurons, and over hundreds studies have been published on TDP-43 and its role in ALS and FTLD, suggesting that TDP-43 is a critical protein in these neurodegenerative diseases. However, the physiological function of TDP-43 and underlying mechanism to cause neurodegeneration are still elusive. To address these questions, we have showed that targeted depletion of TDP-43 expression in spinal cord motor neurons caused the ALS-phenotypes in mice. Here, we generate conditional knockout mice in which Tardbp gene is inactivated in higher central nervous systems. In comparison to control mice, the conditional knockout mice show behavior and brain pathological alteration. Furthermore, we found that the abnormal electrophysiology in not only the primary culture of mouse cortical neurons with TDP-43 knockdown, but also in the hippocampal CA1 region of the brain slices from conditional TDP-43 knockout mice. In this study, we demonstrate that TDP-43 plays an important role in the higher central nervous system, and provide some molecular mechanism for further studies to investigate the TDP-43 biological function. Keywords: Electrophysiology, neurodegeneration, in vivo, in vitro, Nuclear protein Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Wu MJ, Wu L, Cheng W and Shen CJ (2016). Loss of TDP-43 function causes neurodegeneration in the mice brain. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00158 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 03 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Mr. Ming-Che J Wu, Academia Sinica, Institute of Molecular Biology, Taipei, Taiwan, mcjameswu@gate.sinica.edu.tw Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ming-Che J Wu Lien-Szu Wu Wei-Cheng Cheng C.-K. J Shen Google Ming-Che J Wu Lien-Szu Wu Wei-Cheng Cheng C.-K. J Shen Google Scholar Ming-Che J Wu Lien-Szu Wu Wei-Cheng Cheng C.-K. J Shen PubMed Ming-Che J Wu Lien-Szu Wu Wei-Cheng Cheng C.-K. J Shen Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.