单核和空间转录组学揭示健康衰老和犬认知功能障碍过程中的小胶质细胞功能改变，这一成果由江西农业大学黄路生小组经过不懈努力而取得。该项研究成果发表在2025年9月15日出版的《国家科学评论》上。

该课题组研究人员提出了一个以snRNA-seq为主题的多区域健康犬脑老化图谱，以及一个以snRNA-seq和Stereo-seq为主题的CCD与非CCD脑图谱。健康大脑衰老过程中的细胞异质性分析显示，胶质细胞经历了最明显的改变，在小胶质细胞和星形胶质细胞中发现了以前未被表征的衰老相关亚型，这些亚型有助于髓磷脂的合成。该分析还确定并验证了ZEB1是一种以前未被识别的调节少突胶质细胞分化的转录因子，其表达随着年龄的增长而逐渐下降。CCD的发病机制分析表明齿状回颗粒细胞中小胶质细胞C1QA和CRT的相互作用是突触丧失的重要介质。

此外，与正常衰老犬的小胶质细胞相比，犬CCD在小胶质细胞中代谢淀粉样前体蛋白的能力显着下降。总的来说，这项研究提供了衰老和CCD大脑的单核和空间转录组图谱，为认知功能障碍的分子特征提供了见解。

据介绍，犬类随着年龄的增长会自发发展为阿尔茨海默病（AD）样病理，为研究AD提供了有价值的转化模型。然而，犬大脑在健康衰老和/或犬认知功能障碍（CCD）中的细胞分子功能尚未得到研究。

附：英文原文

Title: Microglial function alterations during healthy ageing and canine cognitive dysfunction revealed by single-nucleus and spatial transcriptomics

Author: Yang, Siyu, Jing, Qiqi, Duan, Wenxin, Huang, Lusheng

Issue&Volume: 2025-09-15

Abstract: Canines, which spontaneously develop Alzheimer's disease (AD) -like pathology with age, serve as valuable translational models for studying AD. However, the cellular molecular functions of the canine brain in healthy ageing and/or canine cognitive dysfunction (CCD) have not yet been studied. Here, we present a multiregional healthy canine brain ageing atlas using snRNA-seq, alongside a CCD versus nonCCD brain atlas generated using both snRNA-seq and Stereo-seq. Cellular heterogeneity analysis during healthy brain ageing revealed that glial cells undergo the most pronounced alterations, with previously uncharacterised ageing-related subtypes identified in microglia and astrocytes that contribute to myelin synthesis. This analysis also identified and validated ZEB1 as a previously unrecognised transcription factor regulating oligodendrocyte differentiation, with expression progressively declining with age. Pathogenetic analysis of CCD revealed that the interaction between microglial C1QA and CRT in dentate gyrus granule cells is a critical mediator of synaptic loss. Furthermore, compared with microglia from normally ageing canines, the canine CCD exhibited a significant decrease in the ability to metabolise amyloid precursor protein in microglia. Overall, this study provides a single-nucleus and spatial transcriptomic atlas of the ageing and CCD brain, offering insights into molecular features underlying cognitive dysfunction.

DOI: 10.1093/nsr/nwaf388

Source: https://dx.doi.org/10.1093/nsr/nwaf388