| First Author | Cho H | Year | 2023 |
| Journal | Mol Psychiatry | PubMed ID | 37365244 |
| Mgi Jnum | J:338253 | Mgi Id | MGI:7510282 |
| Doi | 10.1038/s41380-023-02129-5 | Citation | Cho H, et al. (2023) Adnp-mutant mice with cognitive inflexibility, CaMKIIalpha hyperactivity, and synaptic plasticity deficits. Mol Psychiatry |
| abstractText | ADNP syndrome, involving the ADNP transcription factor of the SWI/SNF chromatin-remodeling complex, is characterized by developmental delay, intellectual disability, and autism spectrum disorders (ASD). Although Adnp-haploinsufficient (Adnp-HT) mice display various phenotypic deficits, whether these mice display abnormal synaptic functions remain poorly understood. Here, we report synaptic plasticity deficits associated with cognitive inflexibility and CaMKIIalpha hyperactivity in Adnp-HT mice. These mice show impaired and inflexible contextual learning and memory, additional to social deficits, long after the juvenile-stage decrease of ADNP protein levels to ~10% of the newborn level. The adult Adnp-HT hippocampus shows hyperphosphorylated CaMKIIalpha and its substrates, including SynGAP1, and excessive long-term potentiation that is normalized by CaMKIIalpha inhibition. Therefore, Adnp haploinsufficiency in mice leads to cognitive inflexibility involving CaMKIIalpha hyperphosphorylation and excessive LTP in adults long after its marked expressional decrease in juveniles. |
