Age-related metabolic and neurodegenerative changes in SAMP8 mice

0563881 - FGÚ 2023 RIV US eng J - Journal Article
Pačesová, A. - Holubová, M. - Hrubá, L. - Strnadová, V. - Neprašová, B. - Pelantová, H. - Kuzma, M. - Železná, B. - Kuneš, Jaroslav - Maletínská, L.
Age-related metabolic and neurodegenerative changes in SAMP8 mice.
Aging. Roč. 14, č. 18 (2022), s. 7300-7327. ISSN 1945-4589
R&D Projects: GA ČR(CZ) GA20-00546S
Institutional support: RVO:67985823
Keywords : Alzheimer’s disease * senescence accelerated mouse prone 8 * neuroinflammation * tau pathology * insulin resistance
OECD category: Physiology (including cytology)
Impact factor: 5.2, year: 2022
Method of publishing: Open access
https://doi.org/10.18632/aging.204284

The most important risk factor for the development of sporadic Alzheimer's disease (AD) is ageing. Senescence accelerated mouse prone 8 (SAMP8) is a model of sporadic AD, with senescence accelerated resistant mouse (SAMR1) as a control. In this study, we aimed to determine the onset of senescence-induced neurodegeneration and the related potential therapeutic window using behavioral experiments, immunohistochemistry and western blotting in SAMP8 and SAMR1 mice at 3, 6 and 9 months of age. The Y-maze revealed significantly impaired working spatial memory of SAMP8 mice from the 6th month. With ageing, increasing plasma concentrations of proinflammatory cytokines in SAMP8 mice were detected as well as significantly increased astrocytosis in the cortex and microgliosis in the brainstem. Moreover, from the 3rd month, SAMP8 mice displayed a decreased number of neurons and neurogenesis in the hippocampus. From the 6th month, increased pathological phosphorylation of tau protein at Thr231 and Ser214 was observed in the hippocampi of SAMP8 mice. In conclusion, changes specific for neurodegenerative processes were observed between the 3rd and 6th month of age in SAMP8 mice, thus, potential neuroprotective interventions could be applied between these ages.
Permanent Link: https://hdl.handle.net/11104/0335667