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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #169929


item Joseph, James
item Bielinski, Donna
item Fisher, Derek

Submitted to: Society for Neuroscience Abstracts and Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 6/1/2004
Publication Date: 10/23/2004
Citation: Joseph, J.A., Bielinski, D., Fisher, D.R. 2004. Blueberry extract inhibits DA-induced increases in MAPK signaling in Muscarinic M1 and M3-transfected COS-7 cells. Soc.Neurosci. Abs. 2004, 30, 1017.17.

Interpretive Summary: not needed

Technical Abstract: Previous research has indicated that selective vulnerability (SV) to oxidative stress (OS) may be important in determining regional differences in functional declines in neuronal aging. OS SV may involve selective deficits in Ca2+ buffering (Ca2+ recovery time, Ca2+RT, following oxotremorine application) to OS determined in part by receptor subtype, with M1, M2 and M4 AChR showing greater OS induced loss (via DA exposure 4 hrs) of Ca2+RT than that seen in M3 or M5 cells' deficits that were prevented by pre treatment of the OS sensitive cells with blueberry (BB) extract. We assessed whether these OS SV differences might involve differential patterns of DA induced PKC', PKC', and/or CREB activation that could also be altered by BB treatment. Thus, M1 or M3AChR transfected COS 7 cells were exposed to 1mM DA and Ca2+RT (calcium imaging), as well as PKC', PKC' and CREB activation (Western blot analyses) examined. Results showed that, as previously observed, M1 cells exhibited greater decrements in Ca2+RT than M3 cells which were unaffected. M1 cells showed lower baseline levels of PKC','and CREB than M3 cells, and subsequent DA treatment induced a greater % increase in PKC' and PKC' in M1 than M3 cells (e.g., PKC'% increase M1 37%; M3 5%;PKC' M1 30%; M3 2%). BB increased both CREB and PKC' in non DA treated cells but it appeared that BB reduced DA induced increases in CREB (40%) and PKC' (30%) in the M1 transfected cells but had little effect on PKC' (5%). BB treatment reduced PKC' (30%), ' (25%) and CREB (50%) in M3 DA treated cells. Taken together these findings suggest that M1/M3 OSSV differences may involve differential signaling, in both baseline and OS treatment conditions, with M3 cells showing higher basal values and lower DA enhancement of PKCs and CREB. These findings also suggest that BB may antagonize OS effects by lowering activation of these signals,