Affiliations: [a]
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
| [b]
Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA
| [c]
Paul F. Glenn Center for Biology of Aging Research at Mayo Clinic, Mayo Clinic, Rochester, MN, USA
| [d]
Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA
Correspondence:
[*]
Correspondence to: Darren J. Baker, Mayo Clinic, 200 1st ST SW, Rochester, MN 55905, USA; Tel.: +1 507 538 4097; E-mail: [email protected].
Abstract: Background:
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. Objective:
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. Methods:
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. Results:
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. Conclusions:
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.
