| First Author | Sakurai K | Year | 2024 |
| Journal | Transl Psychiatry | Volume | 14 |
| Issue | 1 | Pages | 426 |
| PubMed ID | 39379355 | Mgi Jnum | J:354982 |
| Mgi Id | MGI:7737518 | Doi | 10.1038/s41398-024-03138-w |
| Citation | Sakurai K, et al. (2024) Importin alpha4 deficiency induces psychiatric disorder-related behavioral deficits and neuroinflammation in mice. Transl Psychiatry 14(1):426 |
| abstractText | Importin alpha4, which is encoded by the Kpna4 gene, is a well-characterized nuclear-cytoplasmic transport factor known to mediate transport of transcription factors including NF-kappaB. Here, we report that Kpna4 knock-out (KO) mice exhibit psychiatric disorder-related behavioral abnormalities such as anxiety-related behaviors, decreased social interaction, and sensorimotor gating deficits. Contrary to a previous study predicting attenuated NF-kappaB activity as a result of Kpna4 deficiency, we observed a significant increase in expression levels of NF-kappaB genes and proinflammatory cytokines such as TNFalpha, Il-1beta or Il-6 in the prefrontal cortex or basolateral amygdala of the KO mice. Moreover, examination of inflammatory responses in primary cells revealed that Kpna4 deficient cells have an increased inflammatory response, which was rescued by addition of not only full length, but also a nuclear transport-deficient truncation mutant of importin alpha4, suggesting contribution of its non-transport functions. Furthermore, RNAseq of sorted adult microglia and astrocytes and subsequent transcription factor analysis suggested increases in polycomb repressor complex 2 (PRC2) activity in Kpna4 KO cells. Taken together, importin alpha4 deficiency induces psychiatric disorder-related behavioral deficits in mice, along with an increased inflammatory response and possible alteration of PRC2 activity in glial cells. |
