Hitzemann Robert, Ozburn Angela R, Lockwood Denesa, Phillips Tamara J
Department of Behavioral Neuroscience, Portland Alcohol Research Center, Oregon Health and Science University, Portland, OR, USA.
Veterans Affairs Portland Health Care System, Portland, OR, USA.
Curr Top Behav Neurosci. 2023 Nov 21. doi: 10.1007/7854_2023_455.
Animal genetic models have and will continue to provide important new information about the behavioral and physiological adaptations associated with alcohol use disorder (AUD). This chapter focuses on two models, ethanol preference and drinking in the dark (DID), their usefulness in interrogating brain gene expression data and the relevance of the data obtained to interpret AUD-related GWAS and TWAS studies. Both the animal and human data point to the importance for AUD of changes in synaptic transmission (particularly glutamate and GABA transmission), of changes in the extracellular matrix (specifically including collagens, cadherins and protocadherins) and of changes in neuroimmune processes. The implementation of new technologies (e.g., cell type-specific gene expression) is expected to further enhance the value of genetic animal models in understanding AUD.
动物遗传模型已经并将继续提供有关与酒精使用障碍(AUD)相关的行为和生理适应的重要新信息。本章重点介绍两种模型,即乙醇偏好模型和黑暗中饮酒(DID)模型,它们在分析大脑基因表达数据方面的有用性以及所获得的数据与解释AUD相关的全基因组关联研究(GWAS)和转录组全关联研究(TWAS)的相关性。动物和人类数据均表明,突触传递的变化(特别是谷氨酸和γ-氨基丁酸传递)、细胞外基质的变化(具体包括胶原蛋白、钙黏着蛋白和原钙黏着蛋白)以及神经免疫过程的变化对AUD具有重要意义。预计新技术(例如细胞类型特异性基因表达)的应用将进一步提高遗传动物模型在理解AUD方面的价值。