| First Author | Zhang H | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 4 | Pages | 109522 |
| PubMed ID | 38585660 | Mgi Jnum | J:348975 |
| Mgi Id | MGI:7620842 | Doi | 10.1016/j.isci.2024.109522 |
| Citation | Zhang H, et al. (2024) TDP-43 deficiency in suprachiasmatic nucleus perturbs rhythmicity of neuroactivity in prefrontal cortex. iScience 27(4):109522 |
| abstractText | Individuals within the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum (ALS/FTD) often experience disruptive mental behaviors and sleep-wake disturbances. The hallmark of ALS/FTD is the pathological involvement of TAR DNA-binding protein 43 (TDP-43). Understanding the role of TDP-43 in the circadian clock holds promise for addressing these behavioral abnormalities. In this study, we unveil TDP-43 as a pivotal regulator of the circadian clock. TDP-43 knockdown induces intracellular arrhythmicity, disrupts transcriptional activation regulation, and diminishes clock genes expression. Moreover, our experiments in adult mouse reveal that TDP-43 knockdown, specifically within the suprachiasmatic nucleus (SCN), induces locomotor arrhythmia, arrhythmic c-Fos expression, and depression-like behavior. This observation offers valuable insights into the substantial impact of TDP-43 on the behavioral aberrations associated with ALS/FTD. In summary, our study illuminates the significance of TDP-43 in circadian regulation, shedding light on the circadian regulatory mechanisms that may elucidate the pathological underpinnings of ALS/FTD. |
