Epigallocatechin-3-gallate (EGCG) is a major flavonoid component of green tea that displays antiapoptotic effects in numerous models of neurotoxicity. Although the intrinsic free radical scavenging activity of EGCG likely contributes to its antiapoptotic effect, other modes of action have also been suggested. We systematically analyzed the antiapoptotic action of EGCG in primary cultures of rat cerebellar granule neurons (CGNs). The dose-dependent protective effects of EGCG were determined after coincubation with eight different stimuli that each induced neuronal apoptosis by distinct mechanisms. Under these conditions, EGCG provided significant neuroprotection only from insults that induce apoptosis by causing mitochondrial oxidative stress. Despite this selective antiapoptotic effect, EGCG did not significantly alter the endogenous activities or expression of Mn(2+)- superoxide dismutase, glutathione peroxidase, Nrf2, or Bcl-2. Subfractionation of CGNs after incubation with (3)H-EGCG revealed that a striking 90-95% of the polyphenol accumulated in the mitochondrial fraction. These data demonstrate that EGCG selectively protects neurons from apoptosis induced by mitochondrial oxidative stress. This effect is likely due to accumulation of EGCG in the mitochondria, where it acts locally as a free radical scavenger. These properties of EGCG make it an interesting therapeutic candidate for neurodegenerative diseases involving neuronal apoptosis triggered by mitochondrial oxidative stress.

Two experiments investigated the processes underlying the picture superiority effect on recognition memory. Studied pictures were associated with higher accuracy than studied words, regardless of whether test stimuli were words (Experiment 1) or pictures (Experiment 2). Event-related brain potentials (ERPs) recorded during test suggested that the 300-500 msec FN400 old/new effect, hypothesized to be related to familiarity-based recognition, benefited from study/test congruity, such that it was larger when study and test format remained constant than when they differed. The 500-800 msec parietal old/new effect, hypothesized to be related to recollection, benefited from studying pictures, regardless of test format. The parallel between the accuracy and parietal ERP results suggests that picture superiority may arise from encoding the distinctive attributes of pictures in a manner that enhances their later recollection. Furthermore, when words were tested, opposite effects of studying words versus studying pictures were observed on the FN400 (word > picture) versus parietal (picture > word) old/new effects--providing strong evidence for a crossover interaction between these components that is consistent with a dual-process perspective.

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