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Mbnl2 loss alters novel context processing and impairs object recognition memory
Patients with myotonic dystrophy type I (DM1) demonstrate visuospatial dysfunction and impaired performance in tasks requiring recognition or memory of figures and objects. In DM1, CUG expansion RNAs inactivate the muscleblind-like (MBNL) proteins. We show that constitutive Mbnl2 inactivation in Mbn...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193234/ https://www.ncbi.nlm.nih.gov/pubmed/37216102 http://dx.doi.org/10.1016/j.isci.2023.106732 |
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author | Khandelwal, Abinash Cushman, Jesse Choi, Jongkyu Zhuravka, Irina Rajbhandari, Abha Valiulahi, Parvin Li, Xiandu Zhou, Chenyu Comai, Lucio Reddy, Sita |
author_facet | Khandelwal, Abinash Cushman, Jesse Choi, Jongkyu Zhuravka, Irina Rajbhandari, Abha Valiulahi, Parvin Li, Xiandu Zhou, Chenyu Comai, Lucio Reddy, Sita |
author_sort | Khandelwal, Abinash |
collection | PubMed |
description | Patients with myotonic dystrophy type I (DM1) demonstrate visuospatial dysfunction and impaired performance in tasks requiring recognition or memory of figures and objects. In DM1, CUG expansion RNAs inactivate the muscleblind-like (MBNL) proteins. We show that constitutive Mbnl2 inactivation in Mbnl2(ΔE2/ΔE2) mice selectively impairs object recognition memory in the novel object recognition test. When exploring the context of a novel arena in which the objects are later encountered, the Mbnl2(ΔE2/ΔE2) dorsal hippocampus responds with a lack of enrichment for learning and memory-related pathways, mounting instead transcriptome alterations predicted to impair growth and neuron viability. In Mbnl2(ΔE2/ΔE2) mice, saturation effects may prevent deployment of a functionally relevant transcriptome response during novel context exploration. Post-novel context exploration alterations in genes implicated in tauopathy and dementia are observed in the Mbnl2(ΔE2/ΔE2) dorsal hippocampus. Thus, MBNL2 inactivation in patients with DM1 may alter novel context processing in the dorsal hippocampus and impair object recognition memory. |
format | Online Article Text |
id | pubmed-10193234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-101932342023-05-19 Mbnl2 loss alters novel context processing and impairs object recognition memory Khandelwal, Abinash Cushman, Jesse Choi, Jongkyu Zhuravka, Irina Rajbhandari, Abha Valiulahi, Parvin Li, Xiandu Zhou, Chenyu Comai, Lucio Reddy, Sita iScience Article Patients with myotonic dystrophy type I (DM1) demonstrate visuospatial dysfunction and impaired performance in tasks requiring recognition or memory of figures and objects. In DM1, CUG expansion RNAs inactivate the muscleblind-like (MBNL) proteins. We show that constitutive Mbnl2 inactivation in Mbnl2(ΔE2/ΔE2) mice selectively impairs object recognition memory in the novel object recognition test. When exploring the context of a novel arena in which the objects are later encountered, the Mbnl2(ΔE2/ΔE2) dorsal hippocampus responds with a lack of enrichment for learning and memory-related pathways, mounting instead transcriptome alterations predicted to impair growth and neuron viability. In Mbnl2(ΔE2/ΔE2) mice, saturation effects may prevent deployment of a functionally relevant transcriptome response during novel context exploration. Post-novel context exploration alterations in genes implicated in tauopathy and dementia are observed in the Mbnl2(ΔE2/ΔE2) dorsal hippocampus. Thus, MBNL2 inactivation in patients with DM1 may alter novel context processing in the dorsal hippocampus and impair object recognition memory. Elsevier 2023-04-25 /pmc/articles/PMC10193234/ /pubmed/37216102 http://dx.doi.org/10.1016/j.isci.2023.106732 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Khandelwal, Abinash Cushman, Jesse Choi, Jongkyu Zhuravka, Irina Rajbhandari, Abha Valiulahi, Parvin Li, Xiandu Zhou, Chenyu Comai, Lucio Reddy, Sita Mbnl2 loss alters novel context processing and impairs object recognition memory |
title | Mbnl2 loss alters novel context processing and impairs object recognition memory |
title_full | Mbnl2 loss alters novel context processing and impairs object recognition memory |
title_fullStr | Mbnl2 loss alters novel context processing and impairs object recognition memory |
title_full_unstemmed | Mbnl2 loss alters novel context processing and impairs object recognition memory |
title_short | Mbnl2 loss alters novel context processing and impairs object recognition memory |
title_sort | mbnl2 loss alters novel context processing and impairs object recognition memory |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193234/ https://www.ncbi.nlm.nih.gov/pubmed/37216102 http://dx.doi.org/10.1016/j.isci.2023.106732 |
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