Blueberry Antagonism of C-2 Ceramide Disruption of Ca 2+ Responses and Recovery in MAChR-Transfected COS-7 Cell

Abstract

Research indicates that muscarinic receptors (MAChRs) may show selective declines in sensitivity during aging and Alzheimer's disease (AD), and these decrements may be related to oxidative stress sensitivity. M1AChR – transfected COS-7 cells exhibit greater decrements in Ca²⁺ buffering following oxotremorine-induced depolarization than M3 cells. This loss, induced via dopamine (DA) or amyloid-β (Aβ), is similar to those reported in many studies with respect to aging and AD, but were antagonized by blueberry (BB) treatment. However, they may be exacerbated by ceramide which shows considerable increases in AD and aging. Thus, the effects of DA, Aβ₄₂ and/or BB were assessed on calcium parameters (e.g., calcium buffering) in the presence or absence of ceramide in M1 and M3 transfected cells. Results indicated that while ceramide did not produce profound deficits in calcium buffering, in either M1- or M3-transfected COS-7 cells, decrements were seen in the ability of M1- and M3-transfected cells to initially respond to oxotremorine, regardless of DA or Aβ₄₂ exposure. BB pre-treatment (prior to ceramide) antagonized the ceramide treatment in M1-transfected cells but not M3-transfected cells, where ceramide suppressed BB effects. Results are discussed in terms of the effects on lipid induced changes in plasma membranes.