Wu Bingchen, Castagnola Elisa, Robbins Elaine, Kaminsky Mariya, Sanker Subramaniam, McClung Colleen, Cui Xinyan Tracy
University of Pittsburgh.
Louisiana Tech University.
Res Sq. 2025 Sep 18:rs.3.rs-7403119. doi: 10.21203/rs.3.rs-7403119/v1.
The circadian rhythm regulates physiological and behavioral processes, with disruptions linked to metabolic and neuropsychiatric disorders. Circadian genes play a crucial role in the regulation of dopaminergic signaling, yet the underlying molecular mechanisms remain unclear. This study investigates how the gene modulates dopamine (DA) dynamics using electrochemical DA sensing and molecular profiling. Utilizing carbon fiber electrodes (CFEs) with poly(3,4-ethylenedioxythiophene)/carbon nanotube (PEDOT/CNT) coatings, we measured extracellular DA levels in the striatum of wild-type (WT) and Δ19 mutant mice via square wave voltammetry (SWV). Pharmacological perturbation with raclopride (D2/D3 receptor antagonist) and nomifensine (dopamine reuptake inhibitor) revealed an increased DA receptor sensitivity in Δ19 mice, with a significantly faster DA response to raclopride. Molecular profiling via qRT-PCR showed elevated () expression in the ventral tegmental area (VTA) of Δ19 mice, suggesting increased DA synthesis. Additionally, Δ19 mice exhibited higher expression of D2 and D3 dopamine receptors and () in the VTA, implicating altered dopaminergic and γ-aminobutyric acid (GABA)ergic regulation. These findings highlight the gene's role in DA homeostasis, revealing its impact on neurotransmission.
昼夜节律调节生理和行为过程，其紊乱与代谢和神经精神疾病有关。昼夜节律基因在多巴胺能信号传导的调节中起关键作用，但其潜在的分子机制仍不清楚。本研究使用电化学多巴胺传感和分子谱分析来研究该基因如何调节多巴胺（DA）动态。利用涂覆有聚（3,4 - 乙撑二氧噻吩）/碳纳米管（PEDOT/CNT）的碳纤维电极（CFE），我们通过方波伏安法（SWV）测量了野生型（WT）和Δ19突变小鼠纹状体中的细胞外DA水平。用雷氯必利（D2/D3受体拮抗剂）和诺米芬辛（多巴胺再摄取抑制剂）进行药理学扰动显示，Δ19小鼠的DA受体敏感性增加，对雷氯必利的DA反应明显更快。通过qRT-PCR进行的分子谱分析显示，Δ19小鼠腹侧被盖区（VTA）中的（）表达升高，表明DA合成增加。此外，Δ19小鼠在VTA中表现出更高的D2和D3多巴胺受体以及（）表达，这意味着多巴胺能和γ-氨基丁酸（GABA）能调节发生改变。这些发现突出了该基因在DA稳态中的作用，揭示了其对神经传递的影响。
