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Lack of zinc finger protein 521 upregulates dopamine β-hydroxylase expression in the mouse brain, leading to abnormal behavior.
Life Sci 2019; 231:116559LS

Abstract

AIM

Previously, we reported that mice deficient in most of the Zfp521 coding region (Zfp521Δ/Δ 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 Zfp521Δ/Δ 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 Zfp521Δ/Δ mice. We found that ZFP521 suppresses the expression of dopamine β-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 Zfp521Δ/Δ 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.

Authors+Show Affiliations

Department of Circulatory Physiology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.. Electronic address: nobu@m.ehime-u.ac.jp.Department of Circulatory Physiology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.Department of Circulatory Physiology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.Department of Circulatory Physiology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31200001

Citation

Ohkubo, Nobutaka, et al. "Lack of Zinc Finger Protein 521 Upregulates Dopamine Β-hydroxylase Expression in the Mouse Brain, Leading to Abnormal Behavior." Life Sciences, vol. 231, 2019, p. 116559.
Ohkubo N, Aoto M, Kon K, et al. Lack of zinc finger protein 521 upregulates dopamine β-hydroxylase expression in the mouse brain, leading to abnormal behavior. Life Sci. 2019;231:116559.
Ohkubo, N., Aoto, M., Kon, K., & Mitsuda, N. (2019). Lack of zinc finger protein 521 upregulates dopamine β-hydroxylase expression in the mouse brain, leading to abnormal behavior. Life Sciences, 231, p. 116559. doi:10.1016/j.lfs.2019.116559.
Ohkubo N, et al. Lack of Zinc Finger Protein 521 Upregulates Dopamine Β-hydroxylase Expression in the Mouse Brain, Leading to Abnormal Behavior. Life Sci. 2019 Aug 15;231:116559. PubMed PMID: 31200001.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lack of zinc finger protein 521 upregulates dopamine β-hydroxylase expression in the mouse brain, leading to abnormal behavior. AU - Ohkubo,Nobutaka, AU - Aoto,Mamoru, AU - Kon,Kazunori, AU - Mitsuda,Noriaki, Y1 - 2019/06/11/ PY - 2019/03/07/received PY - 2019/05/22/revised PY - 2019/06/10/accepted PY - 2019/6/15/pubmed PY - 2019/9/20/medline PY - 2019/6/15/entrez KW - Behavior KW - Dopamine KW - Dopamine beta-hydroxylase KW - Noradrenaline KW - Schizophrenia KW - Zinc finger protein 521 SP - 116559 EP - 116559 JF - Life sciences JO - Life Sci. VL - 231 N2 - AIM: Previously, we reported that mice deficient in most of the Zfp521 coding region (Zfp521Δ/Δ 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 Zfp521Δ/Δ 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 Zfp521Δ/Δ mice. We found that ZFP521 suppresses the expression of dopamine β-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 Zfp521Δ/Δ 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. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/31200001/Lack_of_zinc_finger_protein_521_upregulates_dopamine_β-hydroxylase_expression_in_the_mouse_brain,_leading_to_abnormal_behavior L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(19)30485-0 DB - PRIME DP - Unbound Medicine ER -