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比格犬的视觉空间功能:人类衰老和痴呆模型中认知衰退的早期标志物。

Visuospatial function in the beagle dog: an early marker of cognitive decline in a model of human aging and dementia.

作者信息

Studzinski Christa M, Christie Lori-Ann, Araujo Joseph A, Burnham W McIntyre, Head Elizabeth, Cotman Carl W, Milgram Norton W

机构信息

Department of Pharmacology, University of Toronto, 1265 Military Trail, Scarborough, Ont., Canada M1C 1A4.

出版信息

Neurobiol Learn Mem. 2006 Sep;86(2):197-204. doi: 10.1016/j.nlm.2006.02.005. Epub 2006 Apr 17.

Abstract

Visuospatial learning and memory impairments are an early marker for age-related cognitive decline and Alzheimer's disease. Similar to humans, aged dogs show visuospatial learning and memory deficits (). One hundred and nine beagle dogs ranging between 0.25 and 11.99 years were tested on a visuospatial delayed non-matching to position (DNMP) task to better characterize the progression of visuospatial deficits in the dog. Age predicted 48.2% of the variability in learning the DNMP, with dogs ranging from 1 to 11.99 years generally making more errors with increasing age. By contrast, puppies (<1 year) likely were showing developmental deficits, possibly due to an immature prefrontal cortex. Mild visuospatial deficits were detected by 6 years, which precedes the typical onset of amyloid-beta (Abeta) accumulation in the dog brain by two years, and can serve as an early marker for cognitive decline in the dog. These findings suggest that (1) age-related changes in visuospatial function in the dog models that seen in humans, further validating the dog as a model for human aging and dementia; and (2) other mechanisms, such as oxidative stress, soluble Abeta oligomers or cholinergic deficits, are likely contributing to the early impairment.

摘要

视觉空间学习和记忆障碍是与年龄相关的认知衰退和阿尔茨海默病的早期标志。与人类相似,老龄犬也表现出视觉空间学习和记忆缺陷()。对109只年龄在0.25至11.99岁之间的比格犬进行了视觉空间延迟位置匹配(DNMP)任务测试,以更好地描述犬类视觉空间缺陷的进展情况。年龄预测了在学习DNMP过程中48.2%的变异性,1至11.99岁的犬通常随着年龄增长犯更多错误。相比之下,幼犬(<1岁)可能表现出发育缺陷,这可能是由于前额叶皮质不成熟所致。6岁时检测到轻度视觉空间缺陷,这比犬脑内典型的淀粉样β蛋白(Aβ)积累提前两年出现,可作为犬类认知衰退的早期标志。这些发现表明:(1)犬模型中视觉空间功能与年龄相关的变化与人类相似,进一步验证了犬作为人类衰老和痴呆模型的有效性;(2)其他机制,如氧化应激、可溶性Aβ寡聚体或胆碱能缺陷,可能导致早期损伤。

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