Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells
| Autor: | Stouffer, M, Khalaf-Nazzal, R, Cifuentes-Diaz, C, Albertini, G, Bandet, E, Grannec, G, Lavilla, V, Deleuze, J-F, Olaso, R, Nosten-Bertrand, M, Francis, Fiona |
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| Přispěvatelé: | Sorbonne Université (SU), Institut du Fer à Moulin (IFM - Inserm U1270 - SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de la Santé et de la Recherche Médicale (INSERM), Francis, Fiona |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Doublecortin Domain Proteins
Morphology Doublecortin Protein hippocampus DISORDERS [SDV]Life Sciences [q-bio] Golgi Apparatus MOUSE Hippocampus Mice Neurodevelopmental disorder Organelle Animals Mouse knockout Molecular and cellular analysis Mice Knockout Behavior Science & Technology Cortical malformation Pyramidal Cells MICROTUBULE-ASSOCIATED PROTEIN Neuropeptides Neurosciences Mitochondria TRANSLOCATION [SDV] Life Sciences [q-bio] MODEL MICE Neurology NEURONAL MIGRATION Mutation GROWTH SHAPE Neurosciences & Neurology Pyramidal neuron Microtubule-Associated Proteins Life Sciences & Biomedicine LAMINATION |
| Zdroj: | Neurobiology of Disease Neurobiology of Disease, 2022, 168, pp.105702. ⟨10.1016/j.nbd.2022.105702⟩ Neurobiology of Disease, 2022, 168, ⟨10.1016/j.nbd.2022.105702⟩ |
| ISSN: | 0969-9961 1095-953X |
| DOI: | 10.1016/j.nbd.2022.105702⟩ |
| Popis: | 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. ispartof: NEUROBIOLOGY OF DISEASE vol:168 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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