Abstract
Research from our laboratory has indicated that the loss of sensitivity that occurs in several receptor systems as a function of age may be an index of an increasing inability to respond to oxidative stress (OS). This loss occurs partially as a result of altered signal transduction (ST). Assessments have involved determining the nature of age-related reductions in oxotremorine enhancement of K+-evoked dopamine release (K+-ERDA) from superfused striatal slices. Using this model, we have found that 1. Reductions can be restored with in vivo administration of the free-radical trapping agent,N-tert-butyl-α-phenylnitrone (PBN); 2. Decrements in DA release induced by NO or H2O2 from striatal slices from both young and old animals could be restored with α-tocopherol or PBN; 3. ST decrements, such as those seen in aging, could be induced with radiation exposure; and 4. Preincubation of the striatal slices with cholesterol decreased subsequent deleterious effects of NO or OH· on DA release. Thus, cholesterol, which increases in neuronal membranes as a function of age, may function as a potent antioxidant and protectant against neuronal damage. These results suggest that therapeutic efforts to restore cognitive deficits in aging and age-related disease might begin with antioxidant reversal of ST decrements.
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Joseph, J.A., Denisova, N., Villalobos-Molina, R. et al. Oxidative stress and age-related neuronal deficits. Molecular and Chemical Neuropathology 28, 35–40 (1996). https://doi.org/10.1007/BF02815202
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DOI: https://doi.org/10.1007/BF02815202