@article{69651be2bce74c38bec57c9d4705d500,
title = "Mbnl2 loss alters novel context processing and impairs object recognition memory",
abstract = "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 Mbnl2ΔE2/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 Mbnl2ΔE2/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 Mbnl2ΔE2/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 Mbnl2ΔE2/ΔE2 dorsal hippocampus. Thus, MBNL2 inactivation in patients with DM1 may alter novel context processing in the dorsal hippocampus and impair object recognition memory.",
keywords = "Biological sciences, Molecular biology, Molecular mechanism of gene regulation, Neuroscience, Transcriptomics",
author = "Abinash Khandelwal and Jesse Cushman and Jongkyu Choi and Irina Zhuravka and Abha Rajbhandari and Parvin Valiulahi and Xiandu Li and Chenyu Zhou and Lucio Comai and Sita Reddy",
note = "Funding Information: Behavioral studies were carried out in the UCLA Behavioral Core. This study was supported in part by R01NS080547 to S.R. Funding Information: Behavioral studies were carried out in the UCLA Behavioral Core. This study was supported in part by R01NS080547 to S.R. S.R. designed the study, analyzed the data, and wrote the manuscript. S.R. and L.C. jointly supervised this work. J. Cushman and I.Z. carried out the behavioral studies and analyzed the data. J. Cushman, I.Z. and S.R. wrote the sections relevant to the behavioral analysis. X.L. C.Z. J. Choi, and P.V. developed the mouse cohorts and carried out behavioral studies. J. Choi and A.R. developed the RNA-seq libraries. A.K. J. Choi, and S.R. analyzed the RNA-seq data. A.K. J. Cushman, and J. Choi contributed equally to this work. S.R. L.C. J. Cushman, A.K. and J. Choi have verified the underlying data. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = may,
day = "19",
doi = "10.1016/j.isci.2023.106732",
language = "English",
volume = "26",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "5",
}