| First Author | Khandelwal A | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 5 | Pages | 106732 |
| PubMed ID | 37216102 | Mgi Jnum | J:335886 |
| Mgi Id | MGI:7485334 | Doi | 10.1016/j.isci.2023.106732 |
| Citation | Khandelwal A, et al. (2023) Mbnl2 loss alters novel context processing and impairs object recognition memory. iScience 26(5):106732 |
| abstractText | 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(DeltaE2/DeltaE2) 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(DeltaE2/DeltaE2) 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(DeltaE2/DeltaE2) 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(DeltaE2/DeltaE2) dorsal hippocampus. Thus, MBNL2 inactivation in patients with DM1 may alter novel context processing in the dorsal hippocampus and impair object recognition memory. |
