Abnormalities of cerebral oxidative metabolism with aging and their relation to the central noradrenergic system

Cerebral oxidative metabolism was studied in vivo by monitoring redox shifts of cytochrome c oxidase in response to direct electrical stimulation of the cerebral cortex in Fischer-344 rats at 3 and 28 months of age. Such activation results in a transient oxidation of cytochrome oxidase associated with brief increase in local cerebral blood volume. In aged rats, the rates of the transient redox responses of cytochrome oxidase (i.e. initial oxidation followed by re-reduction) are slowed by about 50% in comparison to young rats. Cortical norepinephrine was similar in both age-groups. However, while depletion of cortical norepinephrine causes slowing of the rate of re-reduction in young rats by about 50%, such depletion had no effect on the already slow kinetics of the redox shifts of aged rats. Vascular reactivity to increased metabolic demands, defined by the amplitude ratio of the blood volume increase to the cytochrome oxidation, is increased with age but attenuated by norepinephrine depletion in both age-groups. These results suggest that: (1) cerebral cortical levels of norepinephrine do not decline with age in the Fischer-344 rat; (2) development of an age-related impairment in the capability of cerebral oxidative metabolism to respond to conditions of heightened metabolic demands; (3) such impairment is not worsened by depletion of cerebral norepinephrine; (4) exaggerated vascular reactivity to increased metabolic requirement in aging indicates decreased provision of oxygen and metabolic substrates, and (5) this vascular reactivity is mediated by central noradrenergic mechanisms.