{"file":[{"relation":"main_file","checksum":"b705d3d23d0b424ba29920be7ab64c23","creator":"dernst","file_size":8890818,"access_level":"open_access","file_id":"17398","file_name":"2022_NeurobioDisease_Stouffer.pdf","date_updated":"2024-08-06T06:54:24Z","success":1,"date_created":"2024-08-06T06:54:24Z","content_type":"application/pdf"}],"date_created":"2024-05-29T06:10:05Z","external_id":{"pmid":["35339680"]},"title":"Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells","language":[{"iso":"eng"}],"oa_version":"Published Version","publication_status":"published","type":"journal_article","publication":"Neurobiology of Disease","_id":"17067","status":"public","publisher":"Elsevier","abstract":[{"text":"Human doublecortin (DCX) mutations are associated with severe brain malformations leading to aberrant neuron positioning (heterotopia), intellectual disability and epilepsy. DCX is a microtubule-associated protein which plays a key role during neurodevelopment in neuronal migration and differentiation. Dcx knockout (KO) mice show disorganized hippocampal pyramidal neurons. The CA2/CA3 pyramidal cell layer is present as two abnormal layers and disorganized CA3 KO pyramidal neurons are also more excitable than wild-type (WT) cells. To further identify abnormalities, we characterized Dcx KO hippocampal neurons at subcellular, molecular and ultrastructural levels. Severe defects were observed in mitochondria, affecting number and distribution. Also, the Golgi apparatus was visibly abnormal, increased in volume and abnormally organized. Transcriptome analyses from laser microdissected hippocampal tissue at postnatal day 60 (P60) highlighted organelle abnormalities. Ultrastructural studies of CA3 cells performed in P60 (young adult) and > 9 months (mature) tissue showed that organelle defects are persistent throughout life. Locomotor activity and fear memory of young and mature adults were also abnormal: Dcx KO mice consistently performed less well than WT littermates, with defects becoming more severe with age. Thus, we show that disruption of a neurodevelopmentally-regulated gene can lead to permanent organelle anomalies contributing to abnormal adult behavior.","lang":"eng"}],"date_updated":"2024-08-06T06:57:39Z","citation":{"short":"M.A. Stouffer, R. Khalaf-Nazzal, C. Cifuentes-Diaz, G. Albertini, E. Bandet, G. Grannec, V. Lavilla, J.-F. Deleuze, R. Olaso, M. Nosten-Bertrand, F. Francis, Neurobiology of Disease 168 (2022).","ista":"Stouffer MA, Khalaf-Nazzal R, Cifuentes-Diaz C, Albertini G, Bandet E, Grannec G, Lavilla V, Deleuze J-F, Olaso R, Nosten-Bertrand M, Francis F. 2022. Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells. Neurobiology of Disease. 168, 105702.","ieee":"M. A. Stouffer <i>et al.</i>, “Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells,” <i>Neurobiology of Disease</i>, vol. 168. Elsevier, 2022.","mla":"Stouffer, Melissa A., et al. “Doublecortin Mutation Leads to Persistent Defects in the Golgi Apparatus and Mitochondria in Adult Hippocampal Pyramidal Cells.” <i>Neurobiology of Disease</i>, vol. 168, 105702, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.nbd.2022.105702\">10.1016/j.nbd.2022.105702</a>.","ama":"Stouffer MA, Khalaf-Nazzal R, Cifuentes-Diaz C, et al. Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells. <i>Neurobiology of Disease</i>. 2022;168. doi:<a href=\"https://doi.org/10.1016/j.nbd.2022.105702\">10.1016/j.nbd.2022.105702</a>","apa":"Stouffer, M. A., Khalaf-Nazzal, R., Cifuentes-Diaz, C., Albertini, G., Bandet, E., Grannec, G., … Francis, F. (2022). Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells. <i>Neurobiology of Disease</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.nbd.2022.105702\">https://doi.org/10.1016/j.nbd.2022.105702</a>","chicago":"Stouffer, Melissa A, R. Khalaf-Nazzal, C. Cifuentes-Diaz, G. Albertini, E. Bandet, G. Grannec, V. Lavilla, et al. “Doublecortin Mutation Leads to Persistent Defects in the Golgi Apparatus and Mitochondria in Adult Hippocampal Pyramidal Cells.” <i>Neurobiology of Disease</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.nbd.2022.105702\">https://doi.org/10.1016/j.nbd.2022.105702</a>."},"month":"06","date_published":"2022-06-15T00:00:00Z","article_number":"105702","has_accepted_license":"1","file_date_updated":"2024-08-06T06:54:24Z","volume":168,"acknowledgement":"We thank Sylvie Dumont for initial aid with laser microdissection and G. Martinez-Lorenzana for experimental help with electron microscopy. We thank the animal experimentation facility and cellular and tissue imaging platforms at the Institut du Fer à Moulin, supported also by the Région Ile de France and the FRC Rotary. The Francis lab was associated with the BioPsy Labex project and the Ecole des Neurosciences de Paris Ile-de-France (ENP) network. Our salaries and lab were supported by Inserm, the Centre national de la recherche scientifique (CNRS) and Sorbonne University. The Francis group obtained the following funding contributing to this project: the European Union (EU- HEALTH-2013, DESIRE, N° 60253), the JTC 2015 Neurodevelopmental Disorders affiliated with the French Agence National de la Recherche (for \r\nNEURON8-Full- 815-006 STEM-MCD, to FF), E-Rare-3, the ERA-Net for Research on Rare Diseases affiliated with the French ANR (ERARE18-049), the European Cooperation on Science and Technology (COST Action CA16118).","day":"15","pmid":1,"intvolume":"       168","article_processing_charge":"Yes","doi":"10.1016/j.nbd.2022.105702","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"article_type":"original","author":[{"last_name":"Stouffer","first_name":"Melissa A","id":"4C9372C4-F248-11E8-B48F-1D18A9856A87","full_name":"Stouffer, Melissa A"},{"first_name":"R.","last_name":"Khalaf-Nazzal","full_name":"Khalaf-Nazzal, R."},{"full_name":"Cifuentes-Diaz, C.","first_name":"C.","last_name":"Cifuentes-Diaz"},{"full_name":"Albertini, G.","first_name":"G.","last_name":"Albertini"},{"full_name":"Bandet, E.","last_name":"Bandet","first_name":"E."},{"full_name":"Grannec, G.","first_name":"G.","last_name":"Grannec"},{"full_name":"Lavilla, V.","first_name":"V.","last_name":"Lavilla"},{"last_name":"Deleuze","first_name":"J.-F.","full_name":"Deleuze, J.-F."},{"last_name":"Olaso","first_name":"R.","full_name":"Olaso, R."},{"last_name":"Nosten-Bertrand","first_name":"M.","full_name":"Nosten-Bertrand, M."},{"last_name":"Francis","first_name":"F.","full_name":"Francis, F."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","quality_controlled":"1","ddc":["570"],"year":"2022","publication_identifier":{"issn":["0969-9961"]},"department":[{"_id":"SiHi"}],"oa":1}