Ament Seth A, Campbell Rianne R, Lobo Mary Kay, Receveur Joseph P, Agrawal Kriti, Borjabad Alejandra, Byrareddy Siddappa N, Chang Linda, Clarke Declan, Emani Prashant, Gabuzda Dana, Gaulton Kyle J, Giglio Michelle, Giorgi Federico M, Gok Busra, Guda Chittibabu, Hadas Eran, Herb Brian R, Hu Wen, Huttner Anita, Ishmam Mohammad R, Jacobs Michelle M, Kelschenbach Jennifer, Kim Dong-Wook, Lee Cheyu, Liu Shuhui, Liu Xiaokun, Madras Bertha K, Mahurkar Anup A, Mash Deborah C, Mukamel Eran A, Niu Meng, O'Connor Richard M, Pagan Chelsea M, Pang Alina P S, Pillai Piya, Repunte-Canonigo Vez, Ruzicka W Brad, Stanley Jay, Tickle Timothy, Tsai Shang-Yi A, Wang Allen, Wills Lauren, Wilson Alyssa M, Wright Susan N, Xu Siwei, Yang Junchen, Zand Maryam, Zhang Le, Zhang Jing, Akbarian Schahram, Buch Shilpa, Cheng Christine S, Corley Michael J, Fox Howard S, Gerstein Mark, Gummuluru Suryaram, Heiman Myriam, Ho Ya-Chi, Kellis Manolis, Kenny Paul J, Kluger Yuval, Milner Teresa A, Moore David J, Morgello Susan, Ndhlovu Lishomwa C, Rana Tariq M, Sanna Pietro Paolo, Satterlee John S, Sestan Nenad, Spector Stephen A, Spudich Serena, Tilgner Hagen U, Volsky David J, White Owen R, Williams Dionne W, Zeng Hongkui
University of Maryland School of Medicine, Baltimore, MD, USA.
Yale School of Medicine, New Haven, CT, USA.
Mol Psychiatry. 2024 Dec;29(12):3950-3961. doi: 10.1038/s41380-024-02620-7. Epub 2024 Jun 15.
Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of the seminal challenges in treating and studying addiction in human populations is the high prevalence of co-morbid conditions, including an increased risk of contracting a human immunodeficiency virus (HIV) infection. Of the ~15 million people who inject drugs globally, 17% are persons with HIV. Conversely, HIV is a risk factor for SUD because chronic pain syndromes, often encountered in persons with HIV, can lead to an increased use of opioid pain medications that in turn can increase the risk for opioid addiction. We hypothesize that SUD and HIV exert shared effects on brain cell types, including adaptations related to neuroplasticity, neurodegeneration, and neuroinflammation. Basic research is needed to refine our understanding of these affected cell types and adaptations. Studying the effects of SUD in the context of HIV at the single-cell level represents a compelling strategy to understand the reciprocal interactions among both conditions, made feasible by the availability of large, extensively-phenotyped human brain tissue collections that have been amassed by the Neuro-HIV research community. In addition, sophisticated animal models that have been developed for both conditions provide a means to precisely evaluate specific exposures and stages of disease. We propose that single-cell genomics is a uniquely powerful technology to characterize the effects of SUD and HIV in the brain, integrating data from human cohorts and animal models. We have formed the Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium to carry out this strategy.
物质使用障碍(SUD)和药物成瘾是对公众健康的重大威胁,不仅影响着数百万与SUD作斗争的个人,还影响着周围的家庭和社区。在人类群体中治疗和研究成瘾的一个关键挑战是共病状况的高流行率,包括感染人类免疫缺陷病毒(HIV)的风险增加。在全球约1500万注射毒品的人中,17%是艾滋病毒感染者。相反,HIV是SUD的一个风险因素,因为HIV感染者经常出现的慢性疼痛综合征会导致阿片类止痛药物的使用增加,进而增加阿片类成瘾的风险。我们假设SUD和HIV对脑细胞类型产生共同影响,包括与神经可塑性、神经退行性变和神经炎症相关的适应性变化。需要进行基础研究以加深我们对这些受影响细胞类型和适应性变化的理解。在单细胞水平上研究HIV背景下SUD的影响是一种有说服力的策略,有助于理解这两种状况之间的相互作用,神经艾滋病研究界积累的大量经过广泛表型分析的人类脑组织样本使这一策略成为可能。此外,针对这两种状况开发的复杂动物模型提供了一种精确评估特定暴露和疾病阶段的方法。我们认为单细胞基因组学是一种独特而强大的技术,可用于表征SUD和HIV在大脑中的影响,整合来自人类队列和动物模型的数据。我们已经组建了HIV背景下的单细胞阿片类反应(SCORCH)联盟来实施这一策略。