Neuronal housekeeping via activation of autophagy by blueberry, strawberry, acai berry and walnut extracts.

Abstract

Age-related neurodegenerative diseases are associated with an increased accumulation of damaged proteins, organelles and increased susceptibility to oxidative stress and inflammation. Our cell culture and animal studies reveal that polyphenolics found in blueberry, strawberry, acai berry and walnuts protect brain cells from oxidative stress and inflammatory insults and improve cognitive and behavioral indices. The current study investigated the rescuing effects of these extracts on neurons through induction of autophagy, a mechanism by which toxic debris is sequestered in the brain. Thus, HT22 hippocampal neuronal cells and BV2 microglial cells were treated with increasing concentrations of berry and walnut extracts. Variable dose responses were observed with the activation of autophagy, assessed via inhibition of mTOR, activation of Beclin1, ATG5 and ATG7; increased clearance of a polyubiquitin-binding protein p62/SQSTM1; and conversion of MAP1-LC3 I to LC3 II. Cells, treated with berry extracts significantly (P<0.05) inhibited mTOR, increased the clearance of p62 and conversion/clearance of MAP1LC3 I to II. More robust clearance of toxic proteins was observed in the BV2 cells than in neurons. Berry extracts reduced LPS-induced NFkB, while activating the autophagy markers Beclin-1, ATG5 and ATG7. Therefore, the current results provide strong insights on the potential effects of berries and walnuts on brain housekeeping to ward off cellular toxic accumulations.

Grant Funding Source: USDA Intramural Grants, ARS agreements