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酒精使用障碍非人灵长类动物模型中微管的成像

Imaging of Microtubules in a Nonhuman Primate Model of Alcohol Use Disorder.

作者信息

Damuka Naresh, Miller Mack D, Krizan Ivan, Bansode Avinash H, Bradley Caleb, Bashetti Nagaraju, Jv Shanmukha Kumar, Galbo-Thomma Lindsey K, Czoty Paul W, Solingapuram Sai Kiran K

机构信息

Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States.

Department of Chemistry, Koneru Lakshmaiah Education Foundation, Vijayawada, Andhra Pradesh 522302, India.

出版信息

ACS Pharmacol Transl Sci. 2025 Apr 8;8(5):1313-1319. doi: 10.1021/acsptsci.4c00682. eCollection 2025 May 9.

Abstract

Microtubules (MTs), as structural components of the cytoskeleton, are vital for axonal transport, information processing, and signaling within the brain. Disruption of MT integrity has been associated with neurological disorders, including alcohol use disorder (AUD). This study used positron emission tomography (PET) imaging with the radiotracer [C]MPC-6827 to investigate alcohol-induced changes in MT dynamics in a nonhuman primate model of AUD. Dynamic PET scans (0-120 min) were conducted in male cynomolgus monkeys ( = 4) before and after ∼7 months of ethanol self-administration (EtOH SA). Quantitative analysis of standardized uptake values and time-activity curves demonstrated a consistent decrease in [C]MPC-6827 uptake across multiple brain regions, particularly in the amygdala, globus pallidus, and substantia innominata. Statistically significant reductions in tracer uptake were observed in early scan windows (15 and 30 min), suggesting compromised MT integrity due to chronic EtOH SA. These findings provide compelling evidence that chronic alcohol consumption induces significant changes in microtubule dynamics, potentially contributing to pathological processes underlying AUD.

摘要

微管(MTs)作为细胞骨架的结构成分,对轴突运输、信息处理以及大脑内的信号传导至关重要。微管完整性的破坏与包括酒精使用障碍(AUD)在内的神经系统疾病有关。本研究使用放射性示踪剂[C]MPC - 6827的正电子发射断层扫描(PET)成像技术,在AUD的非人灵长类动物模型中研究酒精引起的微管动力学变化。在雄性食蟹猴(n = 4)进行约7个月的乙醇自我给药(EtOH SA)前后,进行了动态PET扫描(0 - 120分钟)。对标准化摄取值和时间 - 活性曲线的定量分析表明,多个脑区,特别是杏仁核、苍白球和无名质中,[C]MPC - 6827的摄取持续下降。在早期扫描窗口(15分钟和30分钟)观察到示踪剂摄取有统计学意义的降低,表明慢性EtOH SA导致微管完整性受损。这些发现提供了令人信服的证据,即长期饮酒会引起微管动力学的显著变化,这可能是AUD潜在病理过程的原因。

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