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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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Detalles Bibliográficos
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
Descripción
Sumario: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.