Coenzyme Q(10) supplementation reverses age-related impairments in spatial learning and lowers protein oxidation

Abstract

Coenzyme Q10 (CoQ) is widely available as a dietary supplement and remains under consideration as a treatment for age-associated neurodegenerative conditions. However, no studies have determined if supplementation, initiated relatively late in life, could have beneficial effects on mild functional impairments associated with normal brain aging. Accordingly, the current study assessed the effect of CoQ intake in older mice for which cognitive and psychomotor impairments were already evident. Separate groups of young (3.5 months) and relatively old mice (17.5 months) were fed a control diet or a diet supplemented with low (0.72 mg/g) or high (2.81 mg/g) concentrations of CoQ for 15 weeks. After 6 weeks, the mice were given tests for spatial learning (Morris water maze), spontaneous locomotor activity, motor coordination, and startle reflex. Age-related impairments in cognitive and psychomotor functions were evident in the 17.5-month-old mice fed the control diet, and the low-CoQ diet failed to affect any aspect of the impaired performance. However, in the Morris water maze test, old mice on the high-CoQ diet swam to the safe platform with greater efficiency than the mice on the control diet. The old mice supplemented with the high-CoQ diet did not show improvement when spatial performance was measured using probe trials and failed to show improvement in other tests of behavioral performance. Protein oxidative damage was decreased in the mitochondria from the heart, liver, and skeletal muscle of the high-CoQ-supplemented mice and, to some extent, in the brain mitochondria. Contrasting with the deleterious effect of long-term CoQ supplementation initiated during young adulthood previously published, this study suggests that CoQ improves spatial learning and attenuates oxidative damage when administered in relatively high doses and delayed until early senescence, after age-related declines have occurred. Thus, in individuals with age-associated symptoms of cognitive decline, high-CoQ intake may be beneficial.

Fig. 1

Effects of age and CoQ supplementation on the efficiency of the mice to locate a hidden platform during acquisition, retention, and reversal sessions (top panels). Swim speed was measured during each of the sessions (bottom panels). Each value represents the mean±SEM, n = 7–11

Fig. 2

Effects of age and CoQ supplementation on time spent in a 40-cm annulus during probe trials in swim maze. The percentage of time (±SE) spent in a 40-cm annulus surrounding the target area was calculated when platform was lowered in sessions 2, 4, 6, and 8. Each value represents the mean±SEM, n = 7–11

Fig. 3

Effects of CoQ supplementation on the startle reflex to submaximal (a) and maximal (b) auditory stimuli or low (c), and high (d) shock stimuli as a function of age. Values are mean±SEM, n = 8–13. Asterisk, different from young control group, P < 0.05; number sign, different from control group of the same age, P < 0.05

Fig. 4

Effects of CoQ supplementation on carbonyl concentration in the mitochondria from the heart, brain, liver, and skeletal muscles. Values are mean±SEM, n = 3–10. Asterisk, different from young control group, P < 0.05; number sign, different from control group of the same age, P < 0.05