A diet enriched with plant sterols prevents the memory impairment induced by cholesterol loss in senescence-accelerated mice.
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.
Centro Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
Azucena
A
Pérez-Cañamás
Institut d'Investigacions Biomèdiques de Barcelona, CSIC, Barcelona, Spain.
Sara
S
Sarroca
Centro Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
Carolina
C
Melero-Jerez
Institut d'Investigacions Biomèdiques de Barcelona, CSIC, Barcelona, Spain.
David
D
Porquet
Departament de Psicologia Bàsica, Universitat de Barcelona, Barcelona, Spain.
Joan
J
Sansa
Centro Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain; Unidad de Biofísica CSIC-UPV/EHU, Campus Universidad del País Vasco, Leioa, Spain; IkerBasque, Basque Foundation for Science, Basque Country, Spain.
Shira
S
Knafo
Centro Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
Jose A
JA
Esteban
Institut d'Investigacions Biomèdiques de Barcelona, CSIC, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. Electronic address: coral.sanfeliu@iibb.csic.es.
Coral
C
Sanfeliu
Centro Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain. Electronic address: dledesma@cbm.csic.es.
Maria Dolores
MD
Ledesma
D000375:Aging / Q000378:metabolism* / Q000523:psychology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000172:deficiency* / Q000378:metabolism; D000072556:Cholesterol 24-Hydroxylase / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000517:prevention & control*; D019587:Dietary Supplements; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism; D017774:Long-Term Potentiation; D008297:Male; D008815:Mice, Inbred Strains; D023421:Models, Animal; D010840:Phytosterols / Q000008:administration & dosage*; D053764:Presenilin-1 / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010840:Phytosterols; D053764:Presenilin-1; D002784:Cholesterol; D000072556:Cholesterol 24-Hydroxylase; D053829:Amyloid Precursor Protein Secretases
Aging; Cholesterol; Memory; Plant sterol diet; Presenilin1; SAMP8