围产期和产前酒精暴露损害成年后代纹状体胆碱能功能和认知灵活性。

IF 4.6 2区 医学 Q1 NEUROSCIENCES
William Purvines , Himanshu Gangal , Xueyi Xie , Joseph Ramos , Xuehua Wang , Rajesh Miranda , Jun Wang
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引用次数: 0

摘要

胎儿酒精谱系障碍(FASD)是由围产期酒精暴露(PeAE)和产前酒精暴露(PAE)引起的,其特征是严重的认知障碍,包括认知灵活性降低。尽管胆碱能中间神经元(CINs)在背内侧纹状体(DMS)的认知和行为灵活性中起着关键作用,但它们对FASD神经行为缺陷的贡献尚不清楚。为了解决这一差距,本研究探讨了PeAE和PAE对成年后代的CIN人群和活动、认知灵活性和强迫性饮酒行为的影响。我们首先通过染色纹状体切片来评估胆碱乙酰转移酶(ChAT)的数量,并观察到成年PeAE后代后纹状体的CINs显著减少。通过电生理记录和使用基因编码ACh传感器的活组织共聚焦成像,功能评估显示PeAE和PAE显著降低了DMS中CIN放电活性和乙酰胆碱(ACh)释放。行为上,暴露于peae的后代在适应反向行动-结果偶然性方面表现出明显的缺陷,尽管初始学习能力完好无损。此外,暴露于peae的小鼠表现出强迫性饮酒行为,其特征是对奎宁掺假酒精的消费量增加和偏好。这些发现共同强调了胆碱能信号受损在PeAE和PAE后观察到的认知和行为缺陷中的关键作用。了解这种胆碱能功能障碍为开发有针对性的干预措施提供了有价值的见解,旨在减轻与FASD相关的认知和行为后果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Perinatal and prenatal alcohol exposure impairs striatal cholinergic function and cognitive flexibility in adult offspring
Fetal Alcohol Spectrum Disorder (FASD), caused by perinatal alcohol exposure (PeAE) and prenatal alcohol exposure (PAE), is characterized by significant cognitive impairments, including reduced cognitive flexibility. Despite the critical role of cholinergic interneurons (CINs) in the dorsomedial striatum (DMS) for cognitive and behavioral flexibility, their contribution to neurobehavioral deficits in FASD remains unclear. To address this gap, this research explored the impact of PeAE and PAE on CIN populations and activity, cognitive flexibility, and compulsive drinking behaviors in adult offspring. We first assessed CIN number by staining striatal sections for choline acetyltransferase (ChAT) and observed a significant reduction in CINs within the posterior striatum of adult PeAE offspring. Functional assessments revealed that PeAE and PAE markedly decreased CIN firing activity and reduced acetylcholine (ACh) release in the DMS, as measured by electrophysiology recordings and live-tissue confocal imaging using a genetically encoded ACh sensor. Behaviorally, PeAE offspring exhibited a significant deficit in adapting to reversed action-outcome contingencies despite intact initial learning capabilities. Moreover, PeAE mice exhibited compulsive alcohol drinking behavior, characterized by elevated consumption and preference for quinine-adulterated alcohol. These findings collectively highlight the critical role of impaired cholinergic signaling in the cognitive and behavioral deficits observed following PeAE and PAE. Understanding this cholinergic dysfunction provides valuable insights necessary for developing targeted interventions aimed at mitigating cognitive and behavioral consequences associated with FASD.
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来源期刊
Neuropharmacology
Neuropharmacology 医学-神经科学
CiteScore
10.00
自引率
4.30%
发文量
288
审稿时长
45 days
期刊介绍: Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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