Alzheimer's disease (AD) is a progressive, age-dependent neurodegenerative disorder affecting specific brain regions that control memory and cognitive functions. Epidemiological studies suggest that exercise and dietary antioxidants are beneficial in reducing AD risk. To date, botanical flavonoids are consistently associated with the prevention of age-related diseases. The present study investigated the effects of 4 months of wheel-running exercise, initiated at 2-months of age, in conjunction with the effects of the green tea catechin (-)-epigallocatechin-3-gallate (EGCG) administered orally in the drinking water (50 mg/kg daily) on: 1) behavioral measures: learning and memory performance in the Barnes maze, nest building, open-field, anxiety in the light-dark box; and 2) soluble amyloid-beta (A beta) levels in the cortex and hippocampus in TgCRND8 (Tg) mice. Untreated Tg mice showed hyperactivity, relatively poor nest building behaviors, and deficits in spatial learning in the Barnes maze. Both EGCG and voluntary exercise, separately and in combination, were able to attenuate nest building and Barnes maze performance deficits. Additionally, these interventions lowered soluble A beta(1-42) levels in the cortex and hippocampus. These results, together with epidemiological and clinical studies in humans, suggest that dietary polyphenols and exercise may have beneficial effects on brain health and slow the progression of AD.

Previous work with the TgCRND8 mouse model of Alzheimer’s disease has shown that voluntary exercise implemented for long time periods (5-months) and starting at very young ages (1-month), prior to the development of disease pathology, reduces cognitive impairments; however, approximately 1-month of exercise started at 80-days failed to provide cognitive improvements for male mice. Additionally, research has shown that EGCG, a botanical polyphenol, can reduce amyloid-beta levels, mitigate oxidative stress and reduce some of the cognitive impairments associated with Alzheimer’s disease in the Tg2576 murine model; however, oral administration of EGCG had not been yet evaluated in the TgCRND8 strain. The present study investigated the effects of 4-months of exercise treatment, implemented at the beginning of pathology development (2-months of age), in conjunction with the effects of EGCG treatment on: 1) behavioral measures: learning and memory performance in the Barnes maze, nest building, the open-field, anxiety in the light-dark box, and 2) soluble, amyloid-beta levels in the cortex and hippocampus. Untreated Tg mice showed deficits in nest building behaviors, as well as poor spatial learning in the Barnes maze. Four-months of EGCG and exercise treatment reversed nest building and spatial learning deficits, and lowered soluble, A1-42 levels in the cortex of Tg animals. This research was supported by NIH grant funding (2P01 AG18357).

The recognition of health benefits of phytomedicines and herbal supplements lead to an increased interest to understand the cellular and molecular basis of their biological activities. Apocynin (4-hydroxy-3-methoxy-acetophenone) is a constituent of the Himalayan medicinal herb Picrorhiza kurroa which is regarded as an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, a superoxide-producing enzyme. NADPH oxidase appears to be especially important in the modulation of redox-sensitive signaling pathways and also has been implicated in neuronal dysfunction and degeneration, and neuroinflammmation in diseases ranging from stroke, Alzheimer's and Parkinson's diseases to psychiatric disorders. In this review, we aim to give an overview of current literature on the neuroprotective effects of apocynin in the prevention and treatment of neurodegenerative disorders. Particular attention is given to in vivo studies.

Background: Pluripotent mouse embryonic stem (ES) cells can be induced in vitro to become neural progenitors. Upon transplantation, neural progenitors migrate toward areas of damage and inflammation in the CNS. We tested whether undifferentiated and neuralized mouse ES cells migrate toward media conditioned by glioma cell lines (C6, U87 & N1321) or Stem Cell Factor (SCF).Results: Cell migration assays revealed selective migration by neuralized ES cells to conditioned media as well as to synthetic SCF. Migration of undifferentiated ES cells was extensive, but not significantly different from that of controls (Unconditioned Medium). RT-PCR analysis revealed that all the three tumor cell lines tested synthesized SCF and that both undifferentiated and neuralized ES cells expressed c-kit, the receptor for SCF.Conclusion: Our results demonstrate that undifferentiated ES cells are highly mobile and that neural progenitors derived from ES cells are selectively attracted toward factors produced by gliomas. Given that the glioma cell lines synthesize SCF, SCF may be one of several factors that contribute to the selective migration observed.