| Autor: |
Pačesová A; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague 166 10, Czech Republic., Holubová M; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague 166 10, Czech Republic., Hrubá L; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague 166 10, Czech Republic., Strnadová V; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague 166 10, Czech Republic., Neprašová B; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague 166 10, Czech Republic., Pelantová H; Institute of Microbiology of the Czech Academy of Sciences, Prague 142 00, Czech Republic., Kuzma M; Institute of Microbiology of the Czech Academy of Sciences, Prague 142 00, Czech Republic., Železná B; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague 166 10, Czech Republic., Kuneš J; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague 166 10, Czech Republic.; Institute of Physiology of the Czech Academy of Sciences, Prague 142 00, Czech Republic., Maletínská L; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague 166 10, Czech Republic. |
| Abstrakt: |
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. |
