A central role for acetylcholine in entorhinal cortex function and dysfunction with age in humans and mice.

IF 7.5 1区生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2025-01-30 DOI:10.1016/j.celrep.2025.115249

Mala R Ananth, John D Gardus, Chuan Huang, Nikhil Palekar, Mark Slifstein, Laszlo Zaborszky, Ramin V Parsey, David A Talmage, Christine DeLorenzo, Lorna W Role

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Abstract

Structural and functional changes in the entorhinal cortex (EC) are among the earliest signs of cognitive aging. Here, we ask whether a compromised cholinergic system influences early EC impairments and plays a primary role in EC cognition. We evaluated the relationship between loss of integrity of cholinergic inputs to the EC and cognitive deficits in otherwise healthy humans and mice. Using in vivo imaging (PET/MRI) in older humans and high-resolution imaging in wild-type mice and mice with genetic susceptibility to Alzheimer's disease pathology, we establish that loss of cholinergic input to the EC is, in fact, an early feature in cognitive aging. Through mechanistic studies in mice, we find a central role for EC-projecting cholinergic neurons in the expression of EC-related behaviors. Our data demonstrate that alterations to the cholinergic EC are an early, conserved feature of cognitive aging across species and may serve as an early predictor of cognitive status.

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内耳皮层（EC）的结构和功能变化是认知老化的最早迹象之一。在这里，我们要问的是，胆碱能系统受损是否会影响内黑质皮层的早期损伤，并在内侧皮层认知中扮演主要角色。我们评估了胆碱能输入欧共体的完整性丧失与其他健康人和小鼠认知障碍之间的关系。通过对老年人进行活体成像（PET/MRI），以及对野生型小鼠和阿尔茨海默病遗传易感性小鼠进行高分辨率成像，我们确定了胆碱能输入欧共体的丧失实际上是认知老化的早期特征。通过对小鼠进行机理研究，我们发现欧共体胆碱能神经元在欧共体相关行为的表达中起着核心作用。我们的数据表明，胆碱能EC的改变是不同物种认知衰老的早期保守特征，并可作为认知状态的早期预测指标。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.