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对C57BL/6J小鼠在戒除亚慢性暴饮历史期间海马体和前额叶皮质内蛋白质表达的年龄和性别相关变化进行检测。

Examination of age- and sex-related changes in protein expression within the hippocampus and prefrontal cortex during withdrawal from a subchronic history of binge-drinking in C57BL/6J mice.

作者信息

Jimenez Chavez C Leonardo, Madory Lauren E, Denning Chris J E, Lee Edward C, Nguyen Dylan T, Scheldrup Gavin P, Szumlinski Karen K

机构信息

Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, United States.

Department of Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA, United States.

出版信息

Front Behav Neurosci. 2025 Jul 14;19:1619889. doi: 10.3389/fnbeh.2025.1619889. eCollection 2025.

Abstract

INTRODUCTION

Early-onset binge-drinking and biological sex are critical risk factors for the development of cognitive decline and neurodegeneration associated with Alzheimer's disease and related dementias (ADRDs). Recently, we demonstrated that a prior history of binge-drinking during adolescence induces what appears to be latent (>6 months post-drinking) changes in the expression of glutamate receptors and neuropathology markers within brain regions governing working and spatial memory, many of which precede the manifestation of overt cognitive anomalies.

METHODS

To determine whether alcohol-induced changes in protein expression manifest within the hippocampus and prefrontal cortex at earlier times post-drinking, we conducted immunoblotting on tissue from mice with a subchronic history of binge-drinking (14 days of 2-h access to 10, 20 and 40% ethanol) during either adolescence or adulthood.

RESULTS

We previously reported that this binge-drinking regimen produces mild, age- and sex-selective, changes in working memory and spatial recall when behavior was assayed starting a 1 or 30 days withdrawal. Here, we provide evidence a subchronic binge-drinking history is sufficient to alter the expression of certain glutamate receptors and ADRD-related proteins during the first few months following drinking cessation. Further, these alcohol-induced protein changes are regionally specific and sex-selective.

DISCUSSION

The present results add to our growing understanding of the long-term consequences of adolescent-onset binge-drinking of potential relevance to understanding individual variability in the cognitive consequences of heavy drinking.

摘要

引言

早发性暴饮和生物性别是与阿尔茨海默病及相关痴呆症(ADRDs)相关的认知衰退和神经退行性变发展的关键风险因素。最近,我们证明青少年时期有暴饮史会在控制工作记忆和空间记忆的脑区内诱导谷氨酸受体和神经病理学标志物表达出现看似潜伏性的(饮酒后>6个月)变化,其中许多变化在明显的认知异常表现之前就已出现。

方法

为了确定饮酒后早期海马体和前额叶皮质内是否会出现酒精诱导的蛋白质表达变化,我们对在青少年期或成年期有亚慢性暴饮史(14天,每天2小时可接触10%、20%和40%乙醇)的小鼠组织进行了免疫印迹分析。

结果

我们之前报道,当在戒断1天或30天后检测行为时,这种暴饮方案会在工作记忆和空间回忆方面产生轻度的、年龄和性别选择性的变化。在此,我们提供证据表明,亚慢性暴饮史足以在戒酒后的头几个月内改变某些谷氨酸受体和ADRD相关蛋白的表达。此外,这些酒精诱导的蛋白质变化具有区域特异性和性别选择性。

讨论

目前的结果加深了我们对青少年期开始暴饮的长期后果的理解,这可能与理解大量饮酒对认知影响的个体差异有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcc/12301339/f3d1bbaf7aaa/fnbeh-19-1619889-g001.jpg

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