Mbnl2 loss alters novel context processing and impairs object recognition memory.

Autor:	Khandelwal A; Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA., Cushman J; UCLA Behavioral Testing Core, University of California Los Angeles, Los Angeles, CA 90095-1563, USA., Choi J; Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA., Zhuravka I; UCLA Behavioral Testing Core, University of California Los Angeles, Los Angeles, CA 90095-1563, USA., Rajbhandari A; UCLA Behavioral Testing Core, University of California Los Angeles, Los Angeles, CA 90095-1563, USA., Valiulahi P; Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA., Li X; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA., Zhou C; Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA., Comai L; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA., Reddy S; Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 Apr 25; Vol. 26 (5), pp. 106732. Date of Electronic Publication: 2023 Apr 25 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.106732
Abstrakt:	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. Competing Interests: The authors declare no competing interests. (© 2023 The Author(s).)
Databáze:	MEDLINE
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