| First Author | Ohkubo N | Year | 2019 |
| Journal | Life Sci | Volume | 231 |
| Pages | 116559 | PubMed ID | 31200001 |
| Mgi Jnum | J:289777 | Mgi Id | MGI:6437708 |
| Doi | 10.1016/j.lfs.2019.116559 | Citation | Ohkubo N, et al. (2019) Lack of zinc finger protein 521 upregulates dopamine beta-hydroxylase expression in the mouse brain, leading to abnormal behavior. Life Sci 231:116559 |
| abstractText | AIM: Previously, we reported that mice deficient in most of the Zfp521 coding region (Zfp521(Delta/Delta) mice) displayed abnormal behaviors, including hyperlocomotion and lower anxiety. In this study, we aimed to elucidate the involvement and mechanisms of monoamine variation. MAIN METHODS: First, we compared the levels of dopamine (DA), noradrenaline (NA), and serotonin in the brains of Zfp521(Delta/Delta) and Zfp521(+/+) mice using enzyme-linked immunosorbent assay. Next, we elucidated the mechanisms using quantitative PCR and Western Blotting. Additionally, we administered inhibitory drug to the mice and performed behavioral tests. KEY FINDINGS: Our results showed that the DA level decreased and the NA level increased in Zfp521(Delta/Delta) mice. We found that ZFP521 suppresses the expression of dopamine beta-hydroxylase (DBH), which converts DA into NA. We also demonstrated that paired homeodomain transcription factor 2 and early growth response protein-1, which are the transcription factors for Dbh, were involved in the upregulation of Dbh by ZFP521. The administration of nepicastat, a specific inhibitor of DBH, attenuated the abnormal behaviors of Zfp521(Delta/Delta) mice. SIGNIFICANCE: These results suggest that the lack of ZFP521 upregulates the expression of DBH, which leads to a decrease in the DA level and an increase in the NA level in the brain, resulting in abnormal behaviors. |
