Caloric Restriction Improves Spatial Learning Deficits in Tau Mice

• Published in: Journal of Alzheimer's disease Vol. 98; no. 3; p. 925
• Main Authors: Cogut, Valeria, McNeely, Taylor L, Bussian, Tyler J, Graves, Sara I, Baker, Darren J
• Format: Journal Article
• Language: English
• Published: Netherlands 01-01-2024
• Subjects: Alzheimer Disease - pathology; Animals; Caloric Restriction; Disease Models, Animal; Humans; Male; Maze Learning; Mice; Mice, Transgenic; Neuroinflammatory Diseases; Spatial Learning; tau Proteins - genetics; tau Proteins - pharmacology; Tauopathies - pathology; tauopathy; spatial learning; calorie restriction; Alzheimer’s disease; microglia
• ISSN: 1875-8908
• DOI: 10.3233/JAD-231117

Caloric restriction (CR) has been recognized for its benefits in delaying age-related diseases and extending lifespan. While its effects on amyloid pathology in Alzheimer's disease (AD) mouse models are well-documented, its effects on tauopathy, another hallmark of AD, are less explored.
To assess the impact of a short-term 30% CR regimen on age-dependent spatial learning deficits and pathological features in a tauopathy mouse model.
We subjected male PS19 tau P301S (hereafter PS19) and age-matched wildtype mice from two age cohorts (4.5 and 7.5 months old) to a 6-week 30% CR regimen. Spatial learning performance was assessed using the Barnes Maze test. Tau pathology, neuroinflammation, hippocampal cell proliferation, and neurogenesis were evaluated in the older cohort by immunohistochemical staining and RT-qPCR.
CR mitigated age-dependent spatial learning deficits in PS19 mice but exhibited limited effects on tau pathology and the associated neuroinflammation. Additionally, we found a decrease in hippocampal cell proliferation, predominantly of Iba1+ cells.
Our findings reinforce the cognitive benefits conferred by CR despite its limited modulation of disease pathology. Given the pivotal role of microglia in tau-driven pathology, the observed reduction in Iba1+ cells under CR suggests potential therapeutic implications, particularly if CR would be introduced early in disease progression.