doi:10.1016/j.freeradbiomed.2004.11.014 
Copyright © 2004 Elsevier Inc. All rights reserved.
Original contribution
Concurrent administration of coenzyme Q10 and α-tocopherol improves learning in aged mice
Shelley R. Mcdonalda, Rajindar S. Sohalb and Michael J. Forstera, 
, 
aDepartment of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107, USA
bDepartment of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, CA 90089, USA
Received 27 May 2004;
revised 1 October 2004;
accepted 9 November 2004.
Available online 8 December 2004.
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Abstract
The main purpose of this study was to determine whether supplemental intake of coenzyme Q10 (CoQ) (ubiquinone-10) or α-tocopherol, either alone or together, could improve brain function of aged mice, as reflected in their cognitive or psychomotor performance. Separate groups of aged mice (24 months) were administered either CoQ (123 mg/kg/day), or α-tocopherol acetate (200 mg/kg/day), or both, or the vehicle (soybean oil) via gavage for a period of 14 weeks. Three weeks following the initiation of these treatments, mice were given a battery of age-sensitive behavioral tests for the assessment of learning, recent memory, and psychomotor function. In a test that required the mice to rapidly identify and remember the correct arm of a T-maze, and to respond preemptively in order to avoid an electric shock, the intake of α-tocopherol plus CoQ resulted in more rapid learning compared to the control group. Learning was not significantly improved in the mice receiving CoQ or α-tocopherol alone. None of the treatments resulted in a significant improvement of psychomotor performance in the old mice. In a separate study, treatment with higher doses of CoQ alone (250 or 500 mg/kg/day) for 14 weeks failed to produce effects comparable to those of the combination of α-tocopherol and CoQ. The apparent interaction of CoQ and α-tocopherol treatments is consistent with the previous suggestion, based on biochemical studies, that coenzyme Q and α-tocopherol act in concert. Overall, the findings suggest that concurrent supplementation of α-tocopherol with CoQ is more likely to be effective as a potential treatment for age-related learning deficits than supplementation with CoQ or α-tocopherol alone.
Keywords: C57BL/6 mice; Ubiquinone-10; Vitamin E; Antioxidant; Antioxidant combination; Cognitive decline; Recent memory; Psychmotor function; Free radicals
Abbreviations: CoQ, coenzyme Q10; ubiquinone-10
Fig. 1. Effect of daily intake of either α-tocopherol (200 mg/kg body wt) alone, CoQ (123 mg/kg body wt) alone, CoQ plus α-tocopherol, or the soybean oil vehicle (control) on body weight and survival of male C57BL/6 mice aged 24 months at the time of the initiation of treatment. The left panel shows mean body weight ± SE, averaged within 4-week periods. The right panel shows the Kaplan-Meier probability of survival for the same mice. There was no significant effect of the chronic treatments on body weight [F(3,37) = 0.609, P = 0.613] or survivorship [χ2 = 1.2, P = 0.74].
Fig. 2. Effect of daily intake of either α-tocopherol (200 mg/kg body wt) alone, CoQ (123 mg/kg body wt) alone, CoQ plus α-tocopherol, or the soybean oil vehicle (control) in aged mice on their avoidance behavior and ability to identify the correct goal during discriminated avoidance training. The results are expressed as the mean number (±SE) of stem avoidance responses (upper panels) or correct choice-point turns (lower panels) within the first five trials of each session. The left panels show the mean number per session over the first six sessions (learning phase) whereas the right panels show the mean for the session on which the criterion of reversal performance was met (final session). ANOVA indicated a significant effect of supplementation on avoidance (P = 0.017), but not correct turns (P = 0.301) during the learning phase. No effect of treatment was evident on the final session (all P > 0.208). (*P < 0.05 for individual comparison with control).
Fig. 3. Effects of two different doses of coenzyme Q intake [250 (n = 9) or 500 mg/kg/day (n = 11)] compared with the vehicle (n = 8) on discriminated avoidance learning of old mice. The results are expressed as the mean number (±SE) of stem avoidance responses (upper panels) or correct choice-point turns (lower panels) within the first 5 trials of each session. The left panels show the mean number per session over the first 6 sessions (learning phase) whereas the right panels show the mean for the session on which the criterion of reversal performance was met (final session). ANOVA failed to indicate a significant effect of CoQ dosage during any phase of the testing (all P > 0.325).
Table 1.
Effects of scoenzyme Q and α-tocopherol on balance and psychomotor sperformancea
a All values are the session mean latency in seconds ± SE.
b Running performance during the first session vs maximum running performance achieved after practice (mean latency to fall during the session on which the criterion of stable performance was met).
* P < .05 for individual comparison with control.
Abstract
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