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The Journal of Neuroscience, July 15, 2002, 22(14):6114-6120

Diets Enriched in Foods with High Antioxidant Activity Reverse Age-Induced Decreases in Cerebellar -Adrenergic Function and Increases in Proinflammatory Cytokines

Carmelina Gemma^{1, 2}, Michael H. Mesches^{3, 4}, Boris Sepesi⁴, Kevin Choo⁴, Douglas B. Holmes⁴, and Paula C. Bickford^{1, 2}

¹ James A. Haley Veterans Affairs Medical Center, Tampa, Florida 33612, ² Center for Aging and Brain Repair, Department of Neurosurgery, University of South Florida College of Medicine, Tampa, Florida 33612, ³ Denver Veterans Affairs Medical Center, Denver, Colorado 80220, and ⁴ Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262

Antioxidants and diets supplemented with foods high in oxygen radical absorbance capacity (ORAC) reverse age-related decreases in cerebellar -adrenergic receptor function. We examined whether this effect was related to the antioxidant capacity of the food supplement and whether an antioxidant-rich diet reduced the levels of proinflammatory cytokines in the cerebellum. Aged male Fischer 344 rats were given apple (5 mg dry weight), spirulina (5 mg), or cucumber (5 mg) either in 0.5 ml water by oral gavage or supplied in the rat chow daily for 14 d. Electrophysiologic techniques revealed a significant decrease in -adrenergic receptor function in aged control rats. Spirulina reversed this effect. Apple (a food with intermediate ORAC) had an intermediate effect on cerebellar -adrenergic receptor physiology, and cucumber (low ORAC) had no effect, indicating that the reversal of -adrenergic receptor function decreases might be related to the ORAC dose. The mRNA of the proinflammatory cytokines tumor necrosis factor- (TNF) and TNF was also examined. RNase protection assays revealed increased levels of these cytokines in the aged cerebellum. Spirulina and apple significantly downregulated this age-related increase in proinflammatory cytokines, whereas cucumber had no effect, suggesting that one mechanism by which these diets work is by modulation of an age-related increase in inflammatory responses. Malondialdehyde (MDA) was measured as a marker of oxidative damage. Apple and spirulina but not cucumber decreased MDA levels in the aged rats. In summary, the improved -adrenergic receptor function in aged rats induced by diets rich in antioxidants is related to the ORAC dose, and these diets reduce proinflammatory cytokine levels.

Key words: aging; cerebellum; cytokines; antioxidants; norepinephrine; inflammation

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22146114-07$05.00/0

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