Effects and mechanisms of probucol on aging-related hippocampus-dependent cognitive impairment - 13/11/21
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Abstract |
Background |
In the present study, we aimed to investigate the effects of probucol on aging-related hippocampus-dependent cognitive impairment and explore the potential mechanisms.
Methods |
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.
Results |
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.
Conclusions |
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.
Le texte complet de cet article est disponible en PDF.Highlights |
• | 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. |
Keywords : D-galactose, Probucol, Aging, Hippocampus, Learning and memory
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Vol 144
Article 112266- décembre 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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