Age-related metabolic and neurodegenerative changes in SAMP8 mice

Abstract

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 6 th 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 3 rd month, SAMP8 mice displayed a decreased number of neurons and neurogenesis in the hippocampus. From the 6 th 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 3 rd and 6 th month of age in SAMP8 mice; thus, potential neuroprotective interventions could be applied between these ages.

Dopaminergic neuron loss in mice due to increased levels of wild-type human α-Synuclein only takes place under conditions of accelerated aging

“…Male mice were used for all the experiments. Their body weights at the beginning of the experiments were (average ± SEM): R1 nonTg 31.03 ± 0.75 g, R1 α-SynTg 29.78 ± 0.54 g, P8 nonTg 26.56 ± 0.62 g and P8 α-SynTg 26.90 ± 1.68 g. Experimental groups in SAMP8 strain weighted less than SAMR1 groups at all ages, as it has been previously described 32 .

Figure 1 Experimental design and model validation.

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Chaihu Shugan San ameliorated cognitive deficits through regulating gut microbiota in senescence-accelerated mouse prone 8

“…SAMP8 mice are characterized by an early onset of age-related disorders accompanied by neuronal injury as early as 6 months old ( Pacesova et al, 2022 ). Among all SAMP mouse strains, SAMP8 mice show senescence deterioration in cognitive function compared with senescence-resistant (SAMR1) control mice ( del Valle et al, 2012 ).…”

“…Among all SAMP mouse strains, SAMP8 mice show senescence deterioration in cognitive function compared with senescence-resistant (SAMR1) control mice ( del Valle et al, 2012 ). SAMP8 is a widely used mouse model of aging and dementia ( Takahashi, 2010 ; Pacesova et al, 2022 ). Meanwhile, other AD animal models such as APP/PS1 transgenic mouse, 3XTg AD mouse, and 5XFAD mouse are transgenic mice that mimic histological damages in the brain involved in Aβ or Tau, not reflecting aging-related changes.…”

Constituents, pharmacological activities, pharmacokinetic studies, clinical applications, and safety profile on the classical prescription Kaixinsan

“…More importantly, it was found that cholinergic system dysfunction improvement of KXS was significantly correlated with regulation of the nicotinic acetylcholine receptor CHRNB2. Senescence accelerated mouse prone 8 (SAMP8) was reported to develop typical AD pathologies, such as an abnormal expression of anti-aging factors, inflammation, oxidative stress, tau hyperphosphorylation, amyloid-(A) deposits, abnormal autophagy activity, and endoplasmic reticulum stress ( Andrea et al, 2022 ). Therefore, SAMP8 is widely used and considered as an ideal model for AD research, displaying age-related cognitive decline and memory loss ( Xie et al, 2020 ).…”