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The Effects of Coenzyme Q10 on Mice Behavior

By August 9, 2018August 4th, 2019No Comments

Coenzyme Q10, also known as CoQ10, is a compound that is essential for many daily functions. It’s stored in the mitochondria, the powerhouse of cells. Coenzyme Q10 is an essential element because it is required by every single cell in the body for them to perform at optimal levels. As a powerful antioxidant, coenzyme Q10 also protects cells from free radical damage and harmful microorganisms. As a “coenzyme”, this compound aids in proper digestion of food and other essential nutrients, making absorption effective. Although the body can produce coenzyme Q10 on its own, this ability declines with age. This means that consuming more coenzyme Q10 in order to replenish its levels may benefit overall health. Interestingly, studies on mice show that this powerful nutrient is capable of enhancing behavior through its antidepressant, anti-fatigue, anti-seizure and mood-boosting effect, as well as cognitive-enhancing properties.

Effect on Cognitive Function

Coenzyme Q10 is a powerful antioxidant. It helps protect cells against free radical damage, suggesting that it can also be beneficial in brain health. Studies in mice show that coenzyme Q10 exerts a neuroprotective effect that is necessary for the improvement of cognitive function and prevention of age-related learning and memory deficits.

A study by McDonald et al. assessed the beneficial effects of coenzyme Q10  administration on cognitive function in aged mice.[1] In this study, separate groups of aged mice (24 months) were administered with either coenzyme Q10 (123 mg/kg/day) or soybean oil (control). After three weeks, mice were subjected to undergo T maze test in order to assess learning, recent memory, and psychomotor function. Researchers observed that coenzyme Q10-treated mice were likely to rapidly identify and remember the correct arm of the T maze compared to control, thus avoiding an electrical shock. This result suggests that coenzyme Q10 may help improve cognitive impairments associated with the aging process.

In another study, Sandhir et al. found that coenzyme Q10 improves cognitive decline in post-menopausal mice by modulating mitochondrial functions and oxidative stress.[2] In order to induce cognitive impairment, the mice were subjected to undergo surgical removal of the ovaries (ovariectomy). After four weeks of ovariectomy, all the mice received oral coenzyme Q10 (10 mg/kg body weight) daily for 4 weeks. Researchers observed that the mice were more likely to locate the submerged escape platform in the Morris water maze test, suggesting an improvement in cognitive function. Moreover, upon examination of the brains of the mice, they found that coenzyme Q10 supplementation was able to reverse cognitive impairment by improving mitochondrial electron transport and decreasing levels of free radicals.

In mouse models of Alzheimer’s disease, Dumont et al. reported that coenzyme Q10 supplementation improves cognitive performance by reducing the levels of amyloid beta (an abnormal protein that causes the disease).[3] In this study, mice were given coenzyme Q10 and others were fed with control chow. Spatial learning and memory were assessed using the Morris water maze test while motor function was assessed using the balance beam test. Researchers observed that coenzyme Q10-treated mice performed better at finding the hidden escape platform in the Morris water maze test compared to control. However, there were no significant differences in both groups with regards to performance in the balance beam test – both have difficulties travelling across elevated and thin beams. Finally, when the researchers examined the brains of the mice treated with coenzyme Q10, they observed lower levels of amyloid beta compared to control.

Antidepressant Effect

Depression is one of the most common mental health issues that can significantly affect behavior. There is increasing evidence that coenzyme Q10 supplementation may help combat depression. Various studies on mice support the antidepressant activity of coenzyme Q10.

A study by Aboul-fotouh found that coenzyme Q10 exerts its antidepressant effect by counteracting DNA damage in mice.[4] In this study, mice were subjected to undergo chronic restraint stress (CRS) in order to induce depressive-like behavior. The mice were then injected with coenzyme Q10 (25, 50, 100 and 150 mg/kg/day) for 3 weeks and the forced swim test and open field test were performed. Researchers observed that coenzyme Q10-treated mice displayed lesser “floating behavior” (being immobile with its head above water) in the forced swim test and increased exploratory activity in the open field test compared to control, suggesting an antidepressant effect. Upon examination of the mice’s brains, researchers found that coenzyme Q10-treated mice had lower levels of malondialdehyde (causes DNA damage) compared to control.

In another study, Kagal et al. found that coenzyme Q10 supplementation exerts significant antidepressant effect in both mice and rats.[5] Subjects were grouped into three:

  1. Coenzyme Q10 -treated mice and rats;
  2. Amitriptyline-treated mice and rats (antidepressant drug);
  3. Control.

All groups were then subjected to undergo forced swim test and tail suspension test in order to assess the effects of coenzyme Q10 on depression. Researchers observed that in both coenzyme Q10 and amitriptyline-treated groups, subjects displayed lesser floating behavior in the forced swim test and lesser immobility in the tail suspension test compared to the control group. These results suggest that coenzyme Q10’s antidepressant effect can be on par with the antidepressant drug amitriptyline.

Effect on Anhedonia

Anhedonia is characterized by loss of interest in things and decreased ability to feel pleasure. This condition is a core symptom of major depression, but it can also be associated with other mental health disorders. Evidence suggests that coenzyme Q10 has an anti-anhedonic effect which can help boost mood in mice.

In one study, Aboul-fotouh investigated the effects of chronic coenzyme Q10 treatment in rats with anhedonia.[6] In order to induce anhedonia, all the rats were restrained 6 hours daily for 28 days and were then injected with coenzyme Q10 (50, 100, and 200 mg/kg/day) for 4 weeks. The sucrose preference test was then performed in order to assess the beneficial effects of coenzyme Q10 on anhedonia. In this test, rats who consumed a sweet rewarding drink instead of plain drinking water are considered to be free from anhedonia. Researchers observed that coenzyme Q10-treated rats had increased sucrose preference, body weight, and food intake, which is suggestive of the reversal of anhedonia.

Effect on Locomotor Activity

The aging process can reduce functional capacity, resulting in decreased locomotor activity. Studies in mice show that coenzyme Q10 supplementation can reverse age-related impairments in functional capacity, thus improving locomotion.

A study by Shetty et al. investigated the beneficial effects of coenzyme Q10  supplementation in older mice for which psychomotor impairments were already evident.[7] Separate groups of young (3.5 months) and relatively old mice (17.5 months) were fed with a diet supplemented with low (0.72 mg/g) or high (2.81 mg/g) concentrations of coenzyme Q10,  or a control diet for 15 weeks. After 6 weeks, locomotor activity was assessed using a Digiscan apparatus. This is a test cage that detects the spontaneous activity of each mouse. Researchers observed that young and old mice supplemented with coenzyme Q10 displayed improvements in stable running performance compared to control. Upon completion of the behavioral test, the mice were euthanized and examined. Researchers observed that protein oxidative damage was decreased in the brain, heart, liver, and skeletal muscle of mice supplemented with high doses of coenzyme Q10. These results suggest that coenzyme Q10 may help improve locomotor activity in older mice by decreasing oxidative damage.

Sinatra et al. evaluated the behavioral effects of coenzyme Q10 in young adult male mice (3 months of age) and aged mice (24 months of age) in an open field test.[8] Some mice were treated with coenzyme Q10  and the rest were grouped as the control. Interestingly, researchers observed that both young and aged mice supplemented with coenzyme Q10 had increased exploratory behavior in the open field test compared to control, suggesting an increase in locomotor activity.

Effect on Fatigue

There is also increasing evidence that coenzyme Q10 may help relieve fatigue in mice. Studies suggest that coenzyme Q10 exerts its anti-fatigue effect through various important mechanisms.

Depletion of liver glycogen stores and increased levels of serum urea nitrogen and lactic acid are major causes of fatigue. In one study, Fu et al. investigated the anti-fatigue effect of coenzyme Q10 in male mice.[9] Some mice were orally given coenzyme Q10  at doses of 0, 1.5, 15, or 45 mg/kg/day for 4 weeks. In order to assess the anti-fatigue effect of coenzyme Q10, mice were subjected to undergo swimming exercise with loads attached to their tails (equal to 5% of their body weights), and the total swimming time until exhaustion was measured. In addition to this, a concentration of serum urea nitrogen, lactic acid, and liver glycogen was measured after exercise. The results of the study showed that mice treated with coenzyme Q10 displayed a significantly prolonged exhaustive swim time, increased liver glycogen contents, and decreased serum urea nitrogen and lactic acid levels, compared to those who did not receive coenzyme Q10. These results suggest that coenzyme Q10 exerts its anti-fatigue effect by increasing liver glycogen content and decreasing serum urea nitrogen and lactic acid levels.

Effect on Seizures

Seizures often lead to loss of consciousness, muscles stiffness, and jerking movements. These symptoms can be debilitating and can negatively affect behavior as well as the overall quality of life. Interestingly, evidence suggests that coenzyme Q10 has an anti-seizure effect which can be beneficial in decreasing the incidence of seizure attacks.

A study by Sattarinezhad et al. investigated the beneficial effects of coenzyme Q10 on seizures induced by pentylenetetrazole administration or electroshock in mice.[10] In this study, mice were injected with pentylenetetrazole and the other mice were electroshocked in order to induce seizures. Both groups were then given acute or subchronic doses of coenzyme Q10. Researchers observed that only mice who received subchronic doses of coenzyme Q10 had a decreased incidence of seizures induced by pentylenetetrazole or electroshock. These results indicate that subchronic coenzyme Q10 administration in mice may exert an anti-seizure effect.

Conclusion

As a powerful antioxidant, coenzyme Q10 helps protect cells against free radical damage, thereby improving age-related cognitive decline. By improving mitochondrial electron transport, coenzyme Q10 may help reverse cognitive impairment. Aside from age-related cognitive decline, it can also protect against Alzheimer’s disease by reducing the levels of amyloid beta. Coenzyme Q10 also has a potent antidepressant effect that can be in par with antidepressant drugs. In addition, coenzyme Q10 supplementation in mice can reverse anhedonia, thereby leading to improvement in mood. By decreasing oxidative damage, coenzyme Q10 can reverse age-related impairments in functional capacity and improve locomotor activity in mice. By increasing liver glycogen content and decreasing serum urea nitrogen and lactic acid levels, coenzyme Q10 can also fight fatigue and improve exercise performance in mice. Finally, coenzyme Q10 has an anti-seizure effect that is beneficial in decreasing the incidence of attacks. With these positive effects, coenzyme Q10 may potentially be a therapeutic option in patients with cognitive impairment, depression, anhedonia, seizures, and age-related impairments in functional capacity. Furthermore, its anti-fatigue effect may also be beneficial in improving exercise performance,  mood, and quality of life.

References:

  1. Mcdonald SR, Sohal RS, Forster MJ. Concurrent administration of coenzyme Q10 and alpha-tocopherol improves learning in aged mice. Free Radic Biol Med. 2005;38(6):729-36.
  2. Sandhir R, Sethi N, Aggarwal A, Khera A. Coenzyme Q10 treatment ameliorates cognitive deficits by modulating mitochondrial functions in surgically induced menopause. Neurochem Int. 2014;74:16-23.
  3. Dumont M, Kipiani K, Yu F, et al. Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis. 2011;27(1):211-23.
  4. Aboul-fotouh S. Coenzyme Q10 displays antidepressant-like activity with reduction of hippocampal oxidative/nitrosative DNA damage in chronically stressed rats. Pharmacol Biochem Behav. 2013;104:105-12.
  5. Kagal, Urmila & Angadi, Netravathi. (2017). Effect of coenzyme Q10 on depression paradigms in male Wistar rats and Swiss albino mice. National Journal of Physiology, Pharmacy and Pharmacology. 7. 1. 10.5455/njppp.2017.7.0307302042017.
  6. Aboul-fotouh S. Chronic treatment with coenzyme Q10 reverses restraint stress-induced anhedonia and enhances brain mitochondrial respiratory chain and creatine kinase activities in rats. Behav Pharmacol. 2013;24(7):552-60.
  7. Shetty RA, Forster MJ, Sumien N. Coenzyme Q10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation. Age. 2013;35(5):1821-1834. doi:10.1007/s11357-012-9484-9.
  8. Sinatra DS, Sinatra ST, Heyser CJ. The effects of Coenzyme Q10 on locomotor and behavioral activity in young and aged C57BL/6 mice. Biofactors. 2003;18(1-4):283-7.
  9. Fu X, Ji R, Dam J. Antifatigue effect of coenzyme Q10 in mice. J Med Food. 2010;13(1):211-5.
  10. Sattarinezhad E, Shafaroodi H, Sheikhnouri K, Mousavi Z, Moezi L. The effects of coenzyme Q10 on seizures in mice: the involvement of nitric oxide. Epilepsy Behav. 2014;37:36-42.
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