Walnut diet reduces accumulation of polyubiquitinated proteins and inflammation in the brain of aged rats.
An increase in the aggregation of misfolded/damaged polyubiquitinated proteins has been the hallmark of many age-related neurodegenerative diseases. The accumulation of these potentially toxic proteins in brain increases with age, in part due to increased oxidative and inflammatory stresses. Walnuts, rich in omega fatty acids, have been shown to improve memory, cognition and neuronal effects related to oxidative stress (OS) and inflammation (INF) in animals and human trials. The current study found that feeding 19-month-old rats with a 6% or 9% walnut diet significantly reduced the aggregation of polyubiquitinated proteins and activated autophagy, a neuronal housekeeping function, in the striatum and hippocampus. Walnut-fed animals exhibited up-regulation of autophagy through inhibiting phosphorylation of mTOR, up-regulating ATG7 and Beclin 1, and turnover of MAP1BLC3 proteins. The clearance of polyubiquitinated protein aggregates such as p62/SQSTM1 was more profound in hippocampus, a critical region in the brain involved in memory and cognitive performance, than striatum. The clearance of ubiquitinated aggregates was in tandem with significant reductions in OS/INF, as indicated by the levels of P38-MAP kinase and phosphorylations of nuclear factor kappa B and cyclic AMP response element binding protein. The results demonstrate the effectiveness of a walnut-supplemented diet in activating the autophagy function in brain beyond its traditionally known antioxidant and anti-inflammatory benefits.
USDA-ARS, Human Nutrition Research Center on Aging at Tufts University, Boston MA 02111, USA.
Shibu M
SM
Poulose
Donna F
DF
Bielinski
Barbara
B
Shukitt-Hale
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004032:Diet; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control; D031324:Juglans; D008297:Male; D008568:Memory / Q000187:drug effects; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009754:Nuts; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism; D057149:Ubiquitinated Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C561242:Atg7 protein, rat; D000071186:Beclin-1; C512829:Becn1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D005231:Fatty Acids, Unsaturated; D016328:NF-kappa B; D057149:Ubiquitinated Proteins; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes