Coenzyme Q10 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 highCoQ 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 agerelated declines have occurred. Thus, in individuals with age-associated symptoms of cognitive decline, highCoQ intake may be beneficial.

Coenzyme Q10 and α-tocopherol reversed age-associated functional impairments in mice

“…These findings are consistent with previously published studies in our laboratories. When old mice were fed Toc (synthetic form; Sumien et al 2004) and CoQ 10 (powder form; Shetty et al 2013) for short period of time (12–15 weeks vs. 10 weeks in the current study), spatial learning and memory was not affected. However, when a higher dose of CoQ 10 was used (~ 450 mg/kg/d), a significant improvement in spatial learning was observed (Shetty et al 2013).…”

“…Spatial learning and memory were measured using a Morris water maze (MWM) test as described previously (Sumien et al 2009; Shetty et al 2012). A computerized tracking system recorded the length of the path taken by the mouse to reach the platform, as well as the swimming speed (San Diego Instruments, San Diego CA, Model # SA-3).…”

“…The link between oxidative damage and brain aging suggested that experimental interventions attenuating oxidative stress could reverse age-related brain dysfunction, yet rodent studies of antioxidant supplementation have provided inconsistent support for this prediction (Shukitt-Hale et al 1999; Sumien et al 2004; Carney et al 1991; Shetty et al 2012). Moreover, both human and animal studies have suggested that supplementation of a single antioxidant can generate negative outcomes (Sumien et al 2004; Kristal et al 2014; Saremi and Arora 2010).…”

The effects of sigma (σ1) receptor‐selective ligands on muscarinic receptor antagonist‐induced cognitive deficits in mice

“…The active avoidance test is an associative learning test (Olton and Isaacson, 1968;Shetty et al, 2013) where mice were placed in an acrylic T-shaped apparatus with black coloured walls and a clear ceiling. The T-shaped apparatus was divided into three compartments, a stem and two goal arms.…”

“…Spatial learning was evaluated using the Morris water maze (Morris, 1984;D'Hooge and De Deyn, 2001), slightly modified from the method previously reported (Shetty et al, 2013). The apparatus consisted of a white polyethylene circular pool, 120 cm in diameter and 50 cm deep.…”