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Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration

AIM: To delineate the neurogenetic profiles of brain degeneration patterns in myotonic dystrophy type I (DM1). METHODS: In two cohorts of DM1 patients, brain maps of volume loss (VL) and neuropsychological deficits (NDs) were intersected to large‐scale transcriptome maps provided by the Allen Human...

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Autores principales: Jimenez‐Marin, Antonio, Diez, Ibai, Labayru, Garazi, Sistiaga, Andone, Caballero, Maria C., Andres‐Benito, Pol, Sepulcre, Jorge, Ferrer, Isidro, Lopez de Munain, Adolfo, Cortes, Jesus M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292638/
https://www.ncbi.nlm.nih.gov/pubmed/33955002
http://dx.doi.org/10.1111/nan.12725
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author Jimenez‐Marin, Antonio
Diez, Ibai
Labayru, Garazi
Sistiaga, Andone
Caballero, Maria C.
Andres‐Benito, Pol
Sepulcre, Jorge
Ferrer, Isidro
Lopez de Munain, Adolfo
Cortes, Jesus M.
author_facet Jimenez‐Marin, Antonio
Diez, Ibai
Labayru, Garazi
Sistiaga, Andone
Caballero, Maria C.
Andres‐Benito, Pol
Sepulcre, Jorge
Ferrer, Isidro
Lopez de Munain, Adolfo
Cortes, Jesus M.
author_sort Jimenez‐Marin, Antonio
collection PubMed
description AIM: To delineate the neurogenetic profiles of brain degeneration patterns in myotonic dystrophy type I (DM1). METHODS: In two cohorts of DM1 patients, brain maps of volume loss (VL) and neuropsychological deficits (NDs) were intersected to large‐scale transcriptome maps provided by the Allen Human Brain Atlas (AHBA). For validation, neuropathological and RNA analyses were performed in a small series of DM1 brain samples. RESULTS: Twofold: (1) From a list of preselected hypothesis‐driven genes, confirmatory analyses found that three genes play a major role in brain degeneration: dystrophin (DMD), alpha‐synuclein (SNCA) and the microtubule‐associated protein tau (MAPT). Neuropathological analyses confirmed a highly heterogeneous Tau‐pathology in DM1, different to the one in Alzheimer's disease. (2) Exploratory analyses revealed gene clusters enriched for key biological processes in the central nervous system, such as synaptic vesicle recycling, localization, endocytosis and exocytosis, and the serotonin and dopamine neurotransmitter pathways. RNA analyses confirmed synaptic vesicle dysfunction. CONCLUSIONS: The combination of large‐scale transcriptome interactions with brain imaging and cognitive function sheds light on the neurobiological mechanisms of brain degeneration in DM1 that might help define future therapeutic strategies and research into this condition.
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spelling pubmed-92926382022-07-20 Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration Jimenez‐Marin, Antonio Diez, Ibai Labayru, Garazi Sistiaga, Andone Caballero, Maria C. Andres‐Benito, Pol Sepulcre, Jorge Ferrer, Isidro Lopez de Munain, Adolfo Cortes, Jesus M. Neuropathol Appl Neurobiol Original Articles AIM: To delineate the neurogenetic profiles of brain degeneration patterns in myotonic dystrophy type I (DM1). METHODS: In two cohorts of DM1 patients, brain maps of volume loss (VL) and neuropsychological deficits (NDs) were intersected to large‐scale transcriptome maps provided by the Allen Human Brain Atlas (AHBA). For validation, neuropathological and RNA analyses were performed in a small series of DM1 brain samples. RESULTS: Twofold: (1) From a list of preselected hypothesis‐driven genes, confirmatory analyses found that three genes play a major role in brain degeneration: dystrophin (DMD), alpha‐synuclein (SNCA) and the microtubule‐associated protein tau (MAPT). Neuropathological analyses confirmed a highly heterogeneous Tau‐pathology in DM1, different to the one in Alzheimer's disease. (2) Exploratory analyses revealed gene clusters enriched for key biological processes in the central nervous system, such as synaptic vesicle recycling, localization, endocytosis and exocytosis, and the serotonin and dopamine neurotransmitter pathways. RNA analyses confirmed synaptic vesicle dysfunction. CONCLUSIONS: The combination of large‐scale transcriptome interactions with brain imaging and cognitive function sheds light on the neurobiological mechanisms of brain degeneration in DM1 that might help define future therapeutic strategies and research into this condition. John Wiley and Sons Inc. 2021-05-17 2021-12 /pmc/articles/PMC9292638/ /pubmed/33955002 http://dx.doi.org/10.1111/nan.12725 Text en © 2021 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Jimenez‐Marin, Antonio
Diez, Ibai
Labayru, Garazi
Sistiaga, Andone
Caballero, Maria C.
Andres‐Benito, Pol
Sepulcre, Jorge
Ferrer, Isidro
Lopez de Munain, Adolfo
Cortes, Jesus M.
Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration
title Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration
title_full Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration
title_fullStr Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration
title_full_unstemmed Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration
title_short Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration
title_sort transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type i neurodegeneration
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292638/
https://www.ncbi.nlm.nih.gov/pubmed/33955002
http://dx.doi.org/10.1111/nan.12725
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