Mbnl2 loss alters novel context processing and impairs object recognition memory
Abinash Khandelwal,
Jesse Cushman,
Jongkyu Choi,
Irina Zhuravka,
Abha Rajbhandari,
Parvin Valiulahi,
Xiandu Li,
Chenyu Zhou,
Lucio Comai,
Sita Reddy
Affiliations
Abinash Khandelwal
Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Jesse Cushman
UCLA Behavioral Testing Core, University of California Los Angeles, Los Angeles, CA 90095-1563, USA
Jongkyu Choi
Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Irina Zhuravka
UCLA Behavioral Testing Core, University of California Los Angeles, Los Angeles, CA 90095-1563, USA
Abha Rajbhandari
UCLA Behavioral Testing Core, University of California Los Angeles, Los Angeles, CA 90095-1563, USA
Parvin Valiulahi
Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Xiandu Li
. Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Chenyu Zhou
Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Lucio Comai
. Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Corresponding author
Sita Reddy
Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Corresponding author
Summary: 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.
