Submitted to: Journal of Alzheimer's Disease
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/1/2004
Publication Date: 8/1/2004
Citation: Joseph, J.A., Fisher, D.R., Carey, A.N. 2004. Fruit extracts antagonize ab-or da-induced deficits in ca2+ flux in m1-transfected cos-7 cells. Journal of Alzheimer's Disease 6(2004) 403-411. Interpretive Summary: The aged brain may provide "fertile ground" for the development of neurodegenerative diseases such as Alzheimer disease (AD) and certain forms of Parkinson Disease. One reason for this appears to be an inability of the aged brain to protect itself against very reactive molecules called free radicals. Since many, free radicals, require oxygen and produce oxidative stress (OS) which can have a variety of negative effects on the brain and elsewhere in the body. This could eventually lead to a loss of function in neuronal cells, as has been observed in aging and diseases such as AD. Recently, we showed in cells that different subtypes of neurotransmitter receptors called muscarinic receptors, which are important in the regulation of calcium, respond differently to agents which produce OS. Some of the muscarinic receptor subtypes when placed in cells increased sensitivity to agents which produce OS, such as dopamine. This caused the cells to lose their ability to regulate calcium levels when they were stimulated. Interestingly, similar effects were seen when we used an amyloid beta (Abeta) peptide to produce OS in the cells. This peptide makes up the characteristic plaques in the brains of AD patients. A large number of studies have shown that this peptide is toxic in cells, and may have similar toxic effects in the brain. However, we found in this study that when we assessed the effectiveness of fruit extracts that were high in antioxidant activity (blueberry, BB, boysenberry, BY; cranberry, CB; black currant, BC; strawberry, SB; dried plums, DP; and grape, (GR) on the toxic effects of A-beta and dopamine, we were able to block the toxic effects of both A-beta and dopamine on calcium regulation. BB had the greatest effects overall, with other extracts (e.g., BC, GR, and BY) also providing significant protection that was dependent on the oxidative stressor utilized. These findings suggest that the toxic effects of A-beta or DA might be reduced by fruit extracts that are high in antioxidants.
Technical Abstract: Evidence suggests that there is a selective sensitivity to oxidative stress (OSS) among muscarinic receptor (MAChR) subtypes with M1, M2 and M4 showing > OSS than M3 or M5 subtypes in transfected COS-7 cells. This may be important in determining the regional specificity in neuronal aging and Alzheimer Disease (AD). We assessed the effectiveness of blueberry (BB) and other high antioxidant (HA) fruit extracts (boysenberry, BY; cranberry, CB; black currant, BC; strawberry, SB; dried plums, DP; and grape, (GR) on the toxic effects of A-beta 25-35 (100micoMolar, 24 hrs) and DA (1mM, 4 hrs) on calcium buffering (Recovery) following oxotremorine (750 micoMolar) -induced depolarization in M1AChR-transfected COS-7 cells, and on cell viability following DA (4hrs) exposure. The extracts showed differential levels of Recovery protection in comparisons to the non-supplemented controls [DA treatment (BB = GR = BY > CB = BC = DP = SB), A-beta treatment (BB = BC = DP > CB = BY > SB = GR)]. Assessments of DAinduced decrements in viability revealed that all of the extracts had some protective effects (BB = BY = DP > CB = GR = BC = SB). These findings suggest that the putative toxic effects of A-beta or DA might be reduced by HA fruit extracts.