PMID- 30323233 OWN - NLM STAT- MEDLINE DCOM- 20181231 LR - 20191015 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 9 IP - 1 DP - 2018 Oct 15 TI - Modulation of AMPA receptor surface diffusion restores hippocampal plasticity and memory in Huntington's disease models. PG - 4272 LID - 10.1038/s41467-018-06675-3 [doi] LID - 4272 AB - Impaired hippocampal synaptic plasticity contributes to cognitive impairment in Huntington's disease (HD). However, the molecular basis of such synaptic plasticity defects is not fully understood. Combining live-cell nanoparticle tracking and super-resolution imaging, we show that AMPAR surface diffusion, a key player in synaptic plasticity, is disturbed in various rodent models of HD. We demonstrate that defects in the brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling pathway contribute to the deregulated AMPAR trafficking by reducing the interaction between transmembrane AMPA receptor regulatory proteins (TARPs) and the PDZ-domain scaffold protein PSD95. The disturbed AMPAR surface diffusion is rescued by the antidepressant drug tianeptine via the BDNF signaling pathway. Tianeptine also restores the impaired LTP and hippocampus-dependent memory in different HD mouse models. These findings unravel a mechanism underlying hippocampal synaptic and memory dysfunction in HD, and highlight AMPAR surface diffusion as a promising therapeutic target. FAU - Zhang, Hongyu AU - Zhang H AD - Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, 33076, France. hongyu.zhang@uib.no. AD - Interdisciplinary Institute for Neuroscience, Centre National de la Recherche Scientifique (CNRS) UMR 5297, Bordeaux, 33076, France. hongyu.zhang@uib.no. AD - Department of Biomedicine, KG Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Jonas Lies vei 91, N-5009, Bergen, Norway. hongyu.zhang@uib.no. FAU - Zhang, Chunlei AU - Zhang C AD - Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, 33076, France. AD - Interdisciplinary Institute for Neuroscience, Centre National de la Recherche Scientifique (CNRS) UMR 5297, Bordeaux, 33076, France. FAU - Vincent, Jean AU - Vincent J AD - Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, 33076, France. AD - Interdisciplinary Institute for Neuroscience, Centre National de la Recherche Scientifique (CNRS) UMR 5297, Bordeaux, 33076, France. FAU - Zala, Diana AU - Zala D AUID- ORCID: 0000-0002-0052-8011 AD - Institut Curie, CNRS, UMR3306, Inserm, U1005, F-91405, Orsay, France. AD - INSERM U894, Center of Psychiatry and Neuroscience, Paris, France, University Paris-Descartes, Paris, 75006, France. FAU - Benstaali, Caroline AU - Benstaali C AD - Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000, Grenoble, France. AD - INSERM, U1216, F-38000, Grenoble, France. FAU - Sainlos, Matthieu AU - Sainlos M AD - Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, 33076, France. AD - Interdisciplinary Institute for Neuroscience, Centre National de la Recherche Scientifique (CNRS) UMR 5297, Bordeaux, 33076, France. FAU - Grillo-Bosch, Dolors AU - Grillo-Bosch D AUID- ORCID: 0000-0002-8695-5718 AD - Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, 33076, France. AD - Interdisciplinary Institute for Neuroscience, Centre National de la Recherche Scientifique (CNRS) UMR 5297, Bordeaux, 33076, France. FAU - Daburon, Sophie AU - Daburon S AD - Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, 33076, France. AD - Interdisciplinary Institute for Neuroscience, Centre National de la Recherche Scientifique (CNRS) UMR 5297, Bordeaux, 33076, France. FAU - Coussen, Francoise AU - Coussen F AD - Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, 33076, France. AD - Interdisciplinary Institute for Neuroscience, Centre National de la Recherche Scientifique (CNRS) UMR 5297, Bordeaux, 33076, France. FAU - Cho, Yoon AU - Cho Y AD - Institut de Neurosciences Cognitives et Integratives d'Aquitaine, University of Bordeaux, Bordeaux, 33000, France. FAU - David, Denis J AU - David DJ AUID- ORCID: 0000-0002-0506-6688 AD - Universite Paris-Saclay, Univ. Paris-Sud, Faculte de Pharmacie, CESP, INSERM UMRS1178, Chatenay-Malabry, 92296, France. FAU - Saudou, Frederic AU - Saudou F AUID- ORCID: 0000-0001-6107-1046 AD - Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000, Grenoble, France. frederic.saudou@inserm.fr. AD - INSERM, U1216, F-38000, Grenoble, France. frederic.saudou@inserm.fr. AD - CHU Grenoble Alpes, F-38000, Grenoble, France. frederic.saudou@inserm.fr. FAU - Humeau, Yann AU - Humeau Y AD - Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, 33076, France. AD - Interdisciplinary Institute for Neuroscience, Centre National de la Recherche Scientifique (CNRS) UMR 5297, Bordeaux, 33076, France. FAU - Choquet, Daniel AU - Choquet D AUID- ORCID: 0000-0003-4726-9763 AD - Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, 33076, France. daniel.choquet@u-bordeaux.fr. AD - Interdisciplinary Institute for Neuroscience, Centre National de la Recherche Scientifique (CNRS) UMR 5297, Bordeaux, 33076, France. daniel.choquet@u-bordeaux.fr. AD - Bordeaux Imaging Center, CNRS UMS 3420, University of Bordeaux, INSERM US04, 33076, Bordeaux, France. daniel.choquet@u-bordeaux.fr. LA - eng GR - 339541/EC | European Research Council (ERC)/International GR - ANR-10-INBS-04/Agence Nationale de la Recherche (French National Research Agency)/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181015 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, AMPA) RN - 0 (Thiazepines) RN - 0T493YFU8O (tianeptine) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Diffusion MH - Disease Models, Animal MH - Hippocampus/drug effects/metabolism/pathology/*physiopathology MH - Huntington Disease/metabolism/pathology/*physiopathology MH - Long-Term Potentiation/drug effects MH - Memory/drug effects/*physiology MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Neurogenesis/drug effects MH - Neuronal Plasticity/drug effects/*physiology MH - Protein Transport/drug effects MH - Receptor, trkB/metabolism MH - Receptors, AMPA/*metabolism MH - Signal Transduction/drug effects MH - Synapses/drug effects/metabolism MH - Thiazepines/pharmacology PMC - PMC6189172 COIS- The authors declare no competing interests. EDAT- 2018/10/17 06:00 MHDA- 2019/01/01 06:00 PMCR- 2018/10/15 CRDT- 2018/10/17 06:00 PHST- 2016/08/05 00:00 [received] PHST- 2018/09/19 00:00 [accepted] PHST- 2018/10/17 06:00 [entrez] PHST- 2018/10/17 06:00 [pubmed] PHST- 2019/01/01 06:00 [medline] PHST- 2018/10/15 00:00 [pmc-release] AID - 10.1038/s41467-018-06675-3 [pii] AID - 6675 [pii] AID - 10.1038/s41467-018-06675-3 [doi] PST - epublish SO - Nat Commun. 2018 Oct 15;9(1):4272. doi: 10.1038/s41467-018-06675-3.