Dietary and Behavioral Interventions Protect against Age Related Activation of Caspase Cascades in the Canine Brain

作者: Shikha Snigdha , Nicole Berchtold , Giuseppe Astarita , Tommy Saing , Daniele Piomelli

DOI: 10.1371/JOURNAL.PONE.0024652

关键词: Caspase 3Internal medicineEnvironmental enrichmentOxidative stressCaspase-9Behavioral enrichmentImmunologyBiologyProgrammed cell deathCaspaseCeramideEndocrinology

摘要: Lifestyle interventions such as diet, exercise, and cognitive training represent a quietly emerging revolution in the modern approach to counteracting age-related declines brain health. Previous studies our laboratory have shown that long-term dietary supplementation with antioxidants mitochondrial cofactors (AOX) or behavioral enrichment social, cognitive, exercise components (ENR), can effectively improve performance reduce pathology of aged canines, including oxidative damage Aβ accumulation. In this study, we build on extend previous findings by investigating if caspase activation ceramide accumulation frontal cortex, since are common convergence points for Aβ, among other factors associated AD brain. Aged beagles were placed into one four treatment groups: CON – control environment/control AOX– environment/antioxidant ENR enriched AOX/ENR– diet 2.8 years. Following testing, brains removed cortices analyzed monitor levels active 3, 9 their respective cleavage products tau semaphorin7a, ceramides. Our results show activated caspase-3 reduced AOX largest reduction occurring combined AOX/ENR group. Further, reductions correlated errors reversal learning task, which depends cortex function. addition, animals treated an arm showed numbers cells expressing its product semaphorin 7A, while (but not AOX) levels. Overall, these data demonstrate lifestyle curtail pro-degenerative pathways cellular health first regulate higher animal model aging.

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