Cholesterol reduction at the neuronal plasma membrane has been related to age-dependent cognitive decline. We have used senescent-accelerated mice strain 8 (SAMP8), an animal model for aging, to examine the association between cholesterol loss and cognitive impairment and to test strategies to revert this process. We show that the hippocampus of SAMP8 mice presents reduced cholesterol levels and enhanced amount of its degrading enzyme Cyp46A1 (Cyp46) already at 6 months of age. Cholesterol loss accounts for the impaired long-term potentiation in these mice. Plant sterol (PSE)–enriched diet prevents long-term potentiation impairment and cognitive deficits in SAMP8 mice without altering cholesterol levels. PSE diet also reduces the abnormally high amyloid peptide levels in SAMP8 mice brains and restores membrane compartmentalization of presenilin1, the catalytic component of the amyloidogenic γ-secretase. These results highlight the influence of cholesterol loss in age-related cognitive decline and provide with a noninvasive strategy to counteract it. Our results suggest that PSE overtake cholesterol functions in the brain contributing to reduce deleterious consequences of cholesterol loss during aging.
|Number of pages||12|
|Journal||Neurobiology of Aging|
|State||Published - 1 Dec 2016|
Bibliographical noteFunding Information:
The authors thank Guadalupe Pereyra for excellent technical assistance. This work was financed by grants from Ministerio Español de Economía y Competitividad SAF2014-57539-R to Maria Dolores Ledesma, SAF2012-39852-C02-02 to Coral Sanfeliu, CSD2010-00045 to Maria Dolores Ledesma, Coral Sanfeliu, and Jose A. Esteban, and the European Regional Development Fund . Azucena Pérez-Cañamás and Sara Sarroca hold a predoctoral fellowship (FPU) from Ministerio Español de Ciencia e Innovación.
© 2016 Elsevier Inc.
- Plant sterol diet
ASJC Scopus subject areas
- Neuroscience (all)
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology