Rachel C. Rice , Daniela V. Gil , Annalisa M. Baratta , Remy R. Frawley , Shirley Y. Hill , Sean P. Farris , Gregg E. Homanics
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引用次数: 0
摘要
慢性压力和酒精(乙醇)的使用高度相关,可通过分子适应性改变个体的行为,这些适应性并不改变 DNA 序列,而是改变基因表达。最近的大量研究发现,这些非基因组变化可以跨代传递,这可能部分解释了在酒精使用障碍和其他压力相关神经精神疾病的全基因组关联研究中观察到的 "缺失遗传性"。在这篇综述中,我们总结了慢性压力和乙醇暴露非基因组遗传的分子和行为结果,以及可能导致这种遗传性的种系机制。在此过程中,我们概述了进一步研究的必要性,以便(1) 调查父系、母系和双亲非基因组慢性压力和乙醇相关遗传的种系机制;(2) 综合和剖析跨代慢性压力和乙醇暴露;(3) 以癌症为例,确定孕前乙醇暴露导致酒精相关疾病风险的跨代分子结果。详细了解压力和/或乙醇的跨代非基因组效应将有助于深入了解祖先的干扰对跨代疾病风险的影响,并发现改善人类健康的可行目标。
Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior
Chronic stress and alcohol (ethanol) use are highly interrelated and can change an individual’s behavior through molecular adaptations that do not change the DNA sequence, but instead change gene expression. A recent wealth of research has found that these nongenomic changes can be transmitted across generations, which could partially account for the “missing heritability” observed in genome-wide association studies of alcohol use disorder and other stress-related neuropsychiatric disorders. In this review, we summarize the molecular and behavioral outcomes of nongenomic inheritance of chronic stress and ethanol exposure and the germline mechanisms that could give rise to this heritability. In doing so, we outline the need for further research to: (1) Investigate individual germline mechanisms of paternal, maternal, and biparental nongenomic chronic stress- and ethanol-related inheritance; (2) Synthesize and dissect cross-generational chronic stress and ethanol exposure; (3) Determine cross-generational molecular outcomes of preconception ethanol exposure that contribute to alcohol-related disease risk, using cancer as an example. A detailed understanding of the cross-generational nongenomic effects of stress and/or ethanol will yield novel insight into the impact of ancestral perturbations on disease risk across generations and uncover actionable targets to improve human health.
期刊介绍:
Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal.
Basic, translational and clinical research on the following topics as they relate to stress will be covered:
Molecular substrates and cell signaling,
Genetics and epigenetics,
Stress circuitry,
Structural and physiological plasticity,
Developmental Aspects,
Laboratory models of stress,
Neuroinflammation and pathology,
Memory and Cognition,
Motivational Processes,
Fear and Anxiety,
Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse),
Neuropsychopharmacology.