coenzyme-q10 and Cognition-Disorders

Anaesthesia can induce cognitive deficiency in young rodents and monkeys. Mitochondrial dysfunction contributes to the anaesthesia-induced neurotoxicity and neurobehavioural deficits. We therefore assessed the effects of the mitochondrial energy enhancer coenzyme Q 10 (CoQ 10 ) on anaesthesia-induced cognitive deficiency in young mice to investigate the role of mitochondrial dysfunction.. Young mice ( n =134) were randomly assigned into the following four groups: control plus corn oil vehicle (60% oxygen); 3% sevoflurane [2 h daily on postnatal day (P) 6, 7, and 8] plus vehicle; CoQ 10 (50 mg kg -1 ) plus vehicle; or 3% sevoflurane plus CoQ 10 plus vehicle. We determined cognitive function using the Morris water maze at P31-P37. We quantified brain postsynaptic density protein-95, the presynaptic marker synaptophysin, adenosine triphosphate, reactive oxygen species, and mitochondrial membrane potential at P8 and P37.. Coenzyme Q 10 reduced sevoflurane-induced cognitive deficiency in young mice ( F =0.90, P =0.49, n =10-16) and attenuated sevoflurane-induced reductions in postsynaptic density protein-95 ( F =10.56, P <0.01, n =6), synaptophysin ( F =8.44, P =0.01, n =6), adenosine triphosphate ( F =4.34, P =0.05, n =9), and mitochondrial membrane potential ( F =11.43, P <0.01, n =6), but not sevoflurane-induced increases in reactive oxygen species ( F =1.17, P =0.20, n =6), in brain.. These data suggest that CoQ 10 reduces sevoflurane-induced cognitive deficiency by mitigating sevoflurane-induced mitochondrial dysfunction, the reduction in adenosine triphosphate, and synaptic dysfunction. Coenzyme Q 10 could provide an approach to reduce the neurotoxicity of anaesthesia in the developing brain.

Topics: Anesthetics, Inhalation; Animals; Cognition Disorders; Disease Models, Animal; Female; Male; Mice; Mice, Inbred C57BL; Sevoflurane; Ubiquinone; Vitamins

The mechanisms associated with cognitive decline in post-menopausal state driven by loss of ovarian function and reduced estrogen levels are not well understood. The aim of the present study is to investigate the role of mitochondrial dysfunctions in cognitive impairment in post-menopausal state and to evaluate the protective effect of Coenzyme Q10 (CoQ10). A significant decline in cognitive functions was observed in mice after four weeks of ovariectomy as assessed by morris water maze and elevated plus maze. Administration of CoQ10 (10 mg/kg body weight, orally) daily for 4 weeks was found to reverse cognitive deficits observed in ovariectomized (Ovx) mice. The activity of mitochondrial electron transport chain components; NADH: cytochrome c reductase, succinate dehydrogenase and cytochrome c oxidase was significantly reduced in the brain of Ovx mice. This was accompanied by higher levels of ROS, protein carbonyls, lipid peroxidation, mitochondrial swelling and reduced activity of aconitase. The levels of GSH were observed to be significantly lowered resulting in reduced redox ratio (GSH/GSSG) in brain of Ovx mice. Activities of antioxidant enzymes; superoxide dismutase and catalase were also found to be reduced in brain of Ovx animals. CoQ10 supplementation to Ovx mice mitigated the mitochondrial dysfunctions and oxidative stress. Thus, the data indicates that CoQ10 improves cognitive decline in post-menopausal state by modulating mitochondrial functions and oxidative stress.

Topics: Animals; Brain; Cognition Disorders; Electron Transport; Estradiol; Female; Lipid Peroxidation; Maze Learning; Mice; Mitochondria; Mitochondrial Membranes; Ovariectomy; Sexual Maturation; Ubiquinone

The present study was carried out to elucidate the effects of coenzyme Q(10) (CoQ(10)) against cognitive impairments induced by dichlorvos (DDVP). We have previously shown organophosphate, DDVP-induced impairments in neurobehavioral indices viz. rota rod, passive avoidance, and water maze tests. In addition to this, we have also reported that chronic DDVP exposure leads to decreased mitochondrial electron transfer activities of cytochrome oxidase along with altered mitochondrial complexes I-III activity. Administration of CoQ(10) (4.5 mg/kg, i.p. for 12 weeks prior to DDVP administration daily) to DDVP-treated rats improved cognitive performance in passive avoidance task and Morris water maze test. Furthermore, CoQ(10) treatment also reduced oxidative stress (as evident by reduced malondialdehyde, decreased ROS and increased Mn-SOD activity) in DDVP-treated rats' hippocampus region, along with enhanced activity of complexes I-III and complex IV. Electron microscope studies of rat hippocampus mitochondria revealed that CoQ(10) administration leads to near normal physiology of mitochondria with well-defined cristae compared with DDVP-treated animals where enlarged mitochondria with distorted cristae are observed. CoQ(10) administration also attenuated neuronal damage in hippocampus as evident from histopathological studies. These results demonstrate the beneficial effects of CoQ(10) against organophosphate-induced cognitive impairments and hippocampal neuronal degeneration.

Topics: Animals; Avoidance Learning; Cognition Disorders; Dichlorvos; Disease Models, Animal; Drug Administration Schedule; Hippocampus; Male; Maze Learning; Mitochondria; Nerve Degeneration; Oxidative Stress; Proton Pumps; Rats; Rats, Wistar; Ubiquinone; Vitamins

Byproducts of oxidative metabolic reactions could play a role in the pathogenesis of several neurodegenerative diseases (ND) including Alzheimer's disease (AD). We designed a study aimed at investigating a large set of oxidative and antioxidant markers in a sample of patients affected by different forms of dementia or memory impairment.. Serum levels of coenzyme Q(10), malondialdehyde (MDA), the total, oxidized and reduced forms of glutathione (GStot, GSSG and GSH, respectively), reactive oxygen species, anti-oxidized low-density lipoprotein antibodies and antioxidant power (PAO) were investigated in patients affected by AD, mild cognitive impairment, dementia with Lewy bodies and Parkinson's disease with dementia. The patient sample (n = 66) was compared with healthy subjects (HC; n = 62), and a comparison across pathological subgroups was also performed. A multivariate logistic regression model was implemented in order to calculate an algorithm model for predicting the risk of developing a neurodegenerative disorder.. The comparison between the memory deficit (MD) group and HC showed a significant difference for MDA (MD: 6.3 ± 2.8 μg/l; HC: 9.1 ± 4.9 μg/l; p = 1.7 × 10(-6)), GStot (MD: 260.4 ± 62.6 mg/l; HC: 306.5 ± 60.7 mg/l; p = 2.2 × 10(-5)), GSH (MD: 208.9 ± 68.4 mg/l; HC: 295.3 ± 101.3 mg/l; p = 2.2 × 10(-7)) and PAO (MD: 1,066.5 ± 247.7 μmol; HC: 954.9 ± 200.4 μmol; p = 0.8 × 10(-3)). By contrast, no differences in the levels of the studied markers were detected across the different forms of ND. An older age, higher levels of PAO, lower levels of GSH and MDA and the use of cardiovascular or antidepressant drugs were the most important factors associated with the carrier ship of neurodegenerative disorder.. To our knowledge, this is the first study reporting similar oxidative imbalance in different forms of memory impairment, regardless of the specific etiology. Low GSH levels could be considered as a favorable factor in ND; at the same time it could be suggested that higher levels of PAO represent a counteracting mechanism against an increased oxidative stress. The association between vascular risk factors, depressive status and cognitive impairment is in line with findings in the literature.

Topics: Aged; Aged, 80 and over; Antibodies; Case-Control Studies; Cognition Disorders; Female; Glutathione; Humans; Lipoproteins, LDL; Logistic Models; Male; Malondialdehyde; Memory Disorders; Neurodegenerative Diseases; Oxidation-Reduction; Oxidative Stress; Pilot Projects; Reactive Oxygen Species; Ubiquinone

Statins have been suggested to protect against Alzheimer's disease (AD). Recently, however, we reported that aged dogs that underwent chronic statin treatment exhibited cognitive deficits compared with age matched controls. In human studies, blood levels of Coenzyme Q10 (CoQ10) decrease with statin use. CoQ10 is important for proper mitochondrial function and is a powerful antioxidant, two important factors for cognitive health in aging. Thus, the current study tested the hypothesis that CoQ10 levels in the serum and/or parietal cortex are decreased in statin treated dogs and are associated with poorer cognition. Six aged beagles (>8 years) were administered 80 mg/day of atorvastatin for 14.5 months and compared with placebo-treated animals. As predicted, serum CoQ10 was significantly lower in statin-treated dogs. Parietal cortex CoQ10 was not different between the two groups. However, poorer cognition was correlated with lower parietal cortex CoQ10. This study in dogs suggests that serum CoQ10 is reduced with atorvastatin treatment. CoQ10 levels in brain may be linked to impaired cognition in response to atorvastatin, in agreement with previous reports that statins may have a negative impact on cognition in the elderly.

Topics: Aging; Animals; Atorvastatin; Cognition Disorders; Dogs; Female; Heptanoic Acids; Male; Mitochondria; Oxidative Phosphorylation; Oxidative Stress; Parietal Lobe; Pyrroles; Ubiquinone

Increased oxidative stress is implicated in the pathogenesis of Alzheimer's disease (AD). A large body of evidence suggests that mitochondrial dysfunction and increased reactive oxygen species occur prior to amyloid-β (Aβ) deposition. Coenzyme Q10 (CoQ10), a component of the mitochondrial electron transport chain, is well characterized as a neuroprotective antioxidant in animal models and human trials of Huntington's disease and Parkinson's disease, and reduces plaque burden in AβPP/PS1 mice. We now show that CoQ10 reduces oxidative stress and amyloid pathology and improves behavioral performance in the Tg19959 mouse model of AD. CoQ10 treatment decreased brain levels of protein carbonyls, a marker of oxidative stress. CoQ10 treatment resulted in decreased plaque area and number in hippocampus and in overlying cortex immunostained with an Aβ42-specific antibody. Brain Aβ42 levels were also decreased by CoQ10 supplementation. Levels of amyloid-β protein precursor (AβPP) β-carboxyterminal fragments were decreased. Importantly, CoQ10-treated mice showed improved cognitive performance during Morris water maze testing. Our results show decreased pathology and improved behavior in transgenic AD mice treated with the naturally occurring antioxidant compound CoQ10. CoQ10 is well tolerated in humans and may be promising for therapeutic trials in AD.

Topics: Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Behavioral Symptoms; Cognition Disorders; Enzyme-Linked Immunosorbent Assay; Exploratory Behavior; Gene Expression Regulation; Humans; Maze Learning; Mice; Mice, Transgenic; Motor Activity; Motor Skills; Mutation; Neuroblastoma; Peptide Fragments; Protein Carbonylation; Time Factors; Ubiquinone; Vitamins

Conventional antiepileptic drugs fail to adequately control seizures and predispose to cognitive impairment and oxidative stress with chronic usage in a significant proportion of patients with epilepsy. Coenzyme Q10 (CoQ10), an antioxidant compound, exhibits a wide range of therapeutic effects that are attributed to its potent antioxidant capacity. To evaluate the neuroprotective effects of CoQ10 in rats against the observed oxidative stress during seizures induced by pilocarpine, and to study its interactions with the conventional antiepileptic drug phenytoin, two experiments were performed. Experiment 1 was conducted to test the effect of phenytoin, CoQ10, or both on seizure severity and oxidative markers in the pilocarpine model of epilepsy. Experiment 2 was conducted to test the effect of 2 weeks of chronic treatment with phenytoin, CoQ10, or both on oxidative markers and behavioral tests in rats. Overall, CoQ10 reduced the severity of pilocarpine-induced seizures and the severity of oxidative stress. Moreover, it potentiated the antiepileptic effects afforded by phenytoin treatment, with the potential safety and efficacy in ameliorating oxidative stress and cognitive impairment caused by chronic phenytoin therapy. Our findings strongly suggest that CoQ10 can be considered a safe and effective adjuvant to phenytoin therapy in epilepsy both to ameliorate seizure severity and to protect against seizure-induced oxidative damage by reducing the cognitive impairment and oxidative stress associated with chronic use of phenytoin.

Topics: Analysis of Variance; Animals; Anticonvulsants; Avoidance Learning; Catalase; Cognition Disorders; Disease Models, Animal; Drug Synergism; Glutathione; Lipid Peroxidation; Male; Malondialdehyde; Oxidative Stress; Phenytoin; Pilocarpine; Psychomotor Performance; Rats; Rats, Wistar; Reaction Time; Severity of Illness Index; Status Epilepticus; Superoxide Dismutase; Ubiquinone

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a medical illness characterized by disorders in inflammatory and oxidative and nitrosative (IO&NS) pathways.. This paper examines the role of Coenzyme Q10 (CoQ10), a mitochondrial nutrient which acts as an essential cofactor for the production of ATP in mitochondria and which displays significant antioxidant activities. Plasma CoQ10 has been assayed in 58 patients with ME/CFS and in 22 normal controls; the relationships between CoQ10 and the severity of ME/CFS as measured by means of the FibroFatigue (FF) scale were measured.. Plasma CoQ10 was significantly (p=0.00001) lower in ME/CFS patients than in normal controls. Up to 44.8% of patients with ME/CFS had values beneath the lowest plasma CoQ10 value detected in the normal controls, i.e. 490 microg/L. In ME/CFS, there were significant and inverse relationships between CoQ10 and the total score on the FF scale, fatigue and autonomic symptoms. Patients with very low CoQ10 (<390 microg/L) suffered significantly more from concentration and memory disturbances.. The results show that lowered levels of CoQ10 play a role in the pathophysiology of ME/CFS and that symptoms, such as fatigue, and autonomic and neurocognitive symptoms may be caused by CoQ10 depletion. Our results suggest that patients with ME/CFS would benefit from CoQ10 supplementation in order to normalize the low CoQ10 syndrome and the IO&NS disorders. The findings that lower CoQ10 is an independent predictor of chronic heart failure (CHF) and mortality due to CHF may explain previous reports that the mean age of ME/CFS patients dying from CHF is 25 years younger than the age of those dying from CHF in the general population. Since statins significantly decrease plasma CoQ10, ME/CFS should be regarded as a relative contraindication for treatment with statins without CoQ10 supplementation.

Topics: Adult; Autonomic Nervous System; Cognition Disorders; Coronary Artery Disease; Fatigue Syndrome, Chronic; Female; Heart Failure; Humans; Male; Middle Aged; Oxidative Stress; Risk Factors; Ubiquinone; Vasculitis

We tested the hypotheses that supplemental intake of the diet supplement Coenzyme Q10 (CoQ10) could delay brain atrophy in double transgenic amyloid precursor protein (APP) / presenilin 1 (PS1), single transgenic APP and PS1 as well as wild type mice by volume MR image in vivo. One hundred and twelve mice (28 APP/PS1, 28 APP, 28 PS1 and 28 wild types) were studied. Half of each genotype group (n = 14 per group) was treated with CoQ10 2400 mg/kg/day, and the other half with placebo for 60 days. Magnetic resonance (MR) images were used to obtain the volumes of the hemispheres and hippocampi. APP / PS1, APP, PS1 and wild type mice treated with CoQ10 exhibited significantly less atrophy in hemisphere and hippocampus than those receiving placebo. The neuro-protective effect of the CoQ10 on hemispheric volume, and hippocampal volume was related to genotype; greater in APP/PS1 than APP and PS1 mice and less in wild type mice. Our result indicated that CoQ10 may have therapeutic potential in the prevention and treatment of MCI and AD.

Topics: Aging; Animals; Antioxidants; Atrophy; Brain; Cerebrum; Cognition Disorders; Female; Free Radical Scavengers; Hippocampus; Magnetic Resonance Imaging; Male; Mice; Mice, Transgenic; Presenilin-1; Serum Amyloid A Protein; Ubiquinone

Coenzyme Q10 (CoQ10), a peculiar lipophilic antioxidant, is an essential component of the mitochondrial electron-transport chain. It is involved in the manufacturing of adenosine triphosphate (ATP) and has been linked with improving cognitive functions. The present study shows the neuroprotective effect of CoQ10 on cognitive impairments and oxidative damage in hippocampus and cerebral cortex of intracerebroventricular-streptozotocin (ICV-STZ) infused rats. Male Wistar rats (1-year old) were infused bilaterally with an ICV injection of STZ (1.5 mg/kg b.wt., in normal saline), while sham group received vehicle only. After 24 h, the rats were supplemented with CoQ10 (10 mg/kg b.wt. i.p.) for 3 weeks. The learning and memory tests were monitored 2 weeks after the lesioning. STZ-infused rats showed the loss of cognitive performance in Morris water maze and passive avoidance tests. Three weeks after the lesioning, the rats were sacrificed for estimating the contents of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), protein carbonyl (PC), ATP and the activities of glutathione peroxidase (GPx), glutathione reductase (GR), cholineacetyltransferase (ChAT) and acetylcholinesterase (AChE). Significant alteration in the markers of oxidative damage (TBARS, GSH, PC, GPx and GR) and a decline in the level of ATP were observed in the hippocampus and cerebral cortex of ICV-STZ rat. A significant decrease in ChAT activity and a concomitant increase in AChE activity were observed in the hippocampus. However, supplementation with CoQ10 in STZ-infused rats reversed all the parameters significantly. Thus, the study demonstrates that CoQ10 may have a therapeutic importance in the treatment of Alzheimer's type dementia.

Topics: Acetylcholinesterase; Adenosine Triphosphate; Analysis of Variance; Animals; Antioxidants; Avoidance Learning; Cerebral Cortex; Choline O-Acetyltransferase; Coenzymes; Cognition Disorders; Glutathione; Hippocampus; Injections, Intraventricular; Male; Maze Learning; Neuroprotective Agents; Oxidoreductases; Protein Carbonylation; Rats; Rats, Wistar; Statistics, Nonparametric; Streptozocin; Thiobarbituric Acid Reactive Substances; Ubiquinone