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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...

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Autores principales: Khandelwal, Abinash, Cushman, Jesse, Choi, Jongkyu, Zhuravka, Irina, Rajbhandari, Abha, Valiulahi, Parvin, Li, Xiandu, Zhou, Chenyu, Comai, Lucio, Reddy, Sita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
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.
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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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