Differential protection among fractionated blueberry polyphenolic families against DA-, Abeta(42)- and LPS-induced decrements in Ca(2+) buffering in primary hippocampal cells.
It has been postulated that at least part of the loss of cognitive function in aging may be the result of deficits in Ca(2+) recovery (CAR) and increased oxidative/inflammatory (OX/INF) stress signaling. However, previous research showed that aged animals supplemented with blueberry (BB) extract showed fewer deficits in CAR, as well as motor and cognitive functional deficits. A recent subsequent experiment has shown that DA- or Abeta(42)-induced deficits in CAR in primary hippocampal neuronal cells (HNC) were antagonized by BB extract, and (OX/INF) signaling was reduced. The present experiments assessed the most effective BB polyphenol fraction that could protect against OX/INF-induced deficits in CAR, ROS generation, or viability. HNCs treated with BB extract, BB fractions (e.g., proanthocyanidin, PAC), or control medium were exposed to dopamine (DA, 0.1 mM), amyloid beta (Abeta(42), 25 muM) or lipopolysaccharide (LPS, 1 microg/mL). The results indicated that the degree of protection against deficits in CAR varied as a function of the stressor and was generally greater against Abeta(42) and LPS than DA. The whole BB, anthocyanin (ANTH), and PRE-C18 fractions offered the greatest protection, whereas chlorogenic acid offered the lowest protection. Protective capabilities of the various fractions against ROS depended upon the stressor, where the BB extract and the combined PAC (high and low molecular weight) fraction offered the best protection against LPS and Abeta(42) but were less effective against DA-induced ROS. The high and low molecular weight PACs and the ANTH fractions enhanced ROS production regardless of the stressor used, and this reflected increased activation of stress signals (e.g., P38 MAPK). The viability data indicated that the whole BB and combined PAC fraction showed greater protective effects against the stressors than the more fractionated polyphenolic components. Thus, these results suggest that, except for a few instances, the lesser the polyphenolic fractionation, the greater the effects, especially with respect to prevention of ROS and stress signal generation and viability.
Joseph
James A
JA
USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Shukitt-Hale
Barbara
B
Brewer
Gregory J
GJ
Weikel
Karen A
KA
Kalt
Wilhelmina
W
Fisher
Derek R
DR
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D029798:Blueberry Plants / Q000737:chemistry*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D059808:Polyphenols; D020011:Protective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction
D016229:Amyloid beta-Peptides; D005419:Flavonoids; D008070:Lipopolysaccharides; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D020011:Protective Agents; D002118:Calcium; D004298:Dopamine