Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer's disease: three key timepoints through middle-age in females

被引：17

作者：

Bernaud, Victoria E. ^{[1
,2
]}

Bulen, Haidyn L. ^{[1
,2
]}

Pena, Veronica L. ^{[1
,2
]}

Koebele, Stephanie, V ^{[1
,2
]}

Northup-Smith, Steven N. ^{[1
,2
]}

Manzo, Alma A. ^{[1
,2
]}

Sanchez, Maria Valenzuela ^{[1
,2
]}

Opachich, Zorana ^{[1
,2
]}

Ruhland, Ashley M. ^{[1
,2
]}

Bimonte-Nelson, Heather A. ^{[1
,2
]}

机构：

[1] Arizona State Univ, Dept Psychol, Behav Neurosci & Comparat Psychol Div, Arizona Alzheimers Consortium, 950 S McAllister Ave,POB 871104, Tempe, AZ 85287 USA

[2] Arizona Alzheimers Consortium, 4745 N 7th St, Phoenix, AZ 85014 USA

来源：

SCIENTIFIC REPORTS | 2022年 / 12卷 / 01期

关键词：

WORKING-MEMORY; LOAD INCREASES; MOUSE MODEL; SEX; IMPAIRMENT; ESTROGEN; NEUROPATHOLOGY; PERFORMANCE; SEVERITY; DEMENTIA;

D O I：

10.1038/s41598-022-18415-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The Tg F344 rat model of Alzheimer's disease (AD) provides a comprehensive neuropathology presentation, with age-dependent development of tau tangles, amyloid-beta (Afl) plaques, neuronal loss, and increased gliosis. The behavioral trajectory of this model, particularly relating to spatial learning and memory, has yet to be fully characterized. The current experiment evaluated spatial working and reference memory performance, as well as several physiological markers of health, at 3 key age points in female TgF344-AD rats: 6-months, 9-months, and 12-months. At 6 months of age, indications of working and reference memory impairments were observed in transgenic (Tg) rats on the water radial-arm maze, a complex task that requires working and reference memory simultaneously; at 12 months old, Tg impairments were observed for two working memory measures on this task. Notably, no impairments were observed at the 9-month timepoint on this maze. For the Morris maze, a measure of spatial reference memory, Tg rats demonstrated significant impairment relative to wildtype (WT) controls at all 3 age-points. Frontal cortex, entorhina I cortex, and dorsal hippocampus were evaluated for A beta(1-42) expression via western blot in Tg rats only. Analyses of A beta(1-42) expression revealed age-dependent increases in all 3 regions critical to spatial learning and memory. Measures of physiological health, including heart, uterine, and body weights, revealed unique agespecific outcomes for female Tg rats, with the 9-month timepoint identified as critical for further research within the trajectory of AD-like behavior, physiology, and pathology.

引用

页数：17

共 71 条

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