Biomedicine & pharmacotherapy, 2021-12, Vol.144, p.112266-112266, Article 112266
2021
Details
- Autor(en) / Beteiligte
- Titel
- Effects and mechanisms of probucol on aging-related hippocampus-dependent cognitive impairment
- Ist Teil von
- Biomedicine & pharmacotherapy, 2021-12, Vol.144, p.112266-112266, Article 112266
- Ort / Verlag
- France: Elsevier Masson SAS
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- In the present study, we aimed to investigate the effects of probucol on aging-related hippocampus-dependent cognitive impairment and explore the potential mechanisms. D-galactose (100 mg/kg, once daily for 6 weeks) was subcutaneously injected to induce aging in mice. Then the mice were administered with probucol or vehicle once a day for 2 weeks. The hippocampus-related cognition was evaluated with Morris water maze test, novel object recognition test, and contextual fear conditioning test. Moreover, synaptic plasticity was assessed, and RNA-sequencing was applied to further explore the molecular mechanisms. Aging mice induced by D-galactose showed conspicuous learning and memory impairment, which was significantly ameliorated by probucol. Meanwhile, probucol enhanced the spine density and dendritic branches, improved long-term potentiation, and increased the expression of PSD95 of aging mice. Probucol regulated 70 differentially expressed genes compared to D-galactose group, of which 38 genes were upregulated and 32 genes were downregulated. At last, RNA-sequencing results were verified by quantitative reverse transcription-polymerase chain reaction. Probucol improved learning and memory in aging mice through enhancing synaptic plasticity and regulating gene expression, indicating the potential application of probucol to prevent and treat aging-related disorders. •D-gal-induced cognitive dysfunction was reversed by probucol.•Probucol ameliorated the LTP and the expression of PSD95.•Probucol inhibited senescence by regulating the expression of P16 and P53.•Probucol affected the expression of 70 genes as detected by RNA-sequencing.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0753-3322eISSN: 1950-6007DOI: 10.1016/j.biopha.2021.112266Titel-ID: cdi_doaj_primary_oai_doaj_org_article_21440cd05fdf41cebe48d19e2031da17
- Format
- –
- Schlagworte
- Age Factors, Aging, Animals, Behavior, Animal - drug effects, Cellular Senescence - drug effects, Cognition - drug effects, Cognitive Dysfunction - drug therapy, Cognitive Dysfunction - metabolism, Cognitive Dysfunction - physiopathology, Cognitive Dysfunction - psychology, Cyclin-Dependent Kinase Inhibitor p16 - genetics, Cyclin-Dependent Kinase Inhibitor p16 - metabolism, D-galactose, Disease Models, Animal, Disks Large Homolog 4 Protein - metabolism, Fear - drug effects, Gene Expression Regulation, Hippocampus, Hippocampus - drug effects, Hippocampus - metabolism, Hippocampus - pathology, Hippocampus - physiopathology, Learning and memory, Long-Term Potentiation - drug effects, Male, Mice, Mice, Inbred C57BL, Morris Water Maze Test - drug effects, Neurons - drug effects, Neurons - metabolism, Neurons - pathology, Nootropic Agents - pharmacology, Open Field Test - drug effects, Probucol, Probucol - pharmacology, Tumor Suppressor Protein p53 - genetics, Tumor Suppressor Protein p53 - metabolism