Neuroprotective Effects Of Coenzyme Q10 Research Articles

Coenzyme Q10 Ameliorates Neurodegeneration, Mossy Fiber Sprouting, and Oxidative Stress in Intrahippocampal Kainate Model of Temporal Lobe Epilepsy in Rat

Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and the most resistant type to treatment. Novel treatment approaches are strongly required to prevent or even reverse the cellular and molecular mechanisms of epileptogenesis. In this study, we investigated the possible neuroprotective effect of coenzyme Q10 (CoQ10) in an intrahippocampal kainate model of TLE in rat. Kainate injection caused a higher seizure severity during status epilepticus and spontaneous seizure phases, and CoQ10 pretreatment significantly attenuated its severity and incidence rate. Intrahippocampal kainate also led to elevation of malondialdehyde (MDA) and nitrite, and CoQ10 significantly attenuated the increased MDA and nitrite content. In addition, intrahippocampal kainate induced a significant degeneration of neurons in CA1, CA3, and hilar regions of the hippocampus, and CoQ10 significantly attenuated these changes in CA1 and CA3 regions. Timm's staining data showed a robust mossy fiber sprouting (MFS) in dentate gyrus of kainate-lesioned rats and CoQ10 significantly lowered MFS intensity. These data suggest that CoQ10 pretreatment could attenuate spontaneous recurrent seizures and inhibit hippocampal neuronal loss and aberrant MFS in kainate-induced model of TLE in rat, and part of its beneficial effect is due to its potential to mitigate oxidative stress.

WITHDRAWN: Coenzyme Q10 for Parkinson's disease.

A number of preclinical studies in both in vitro and in vivo models of Parkinson's disease have demonstrated that coenzyme Q10 can protect the nigrostriatal dopaminergic system. Some clinical trials have looked at the neuroprotective effects of coenzyme Q10 in patients with early and midstage Parkinson's disease. To assess the evidence from randomized controlled trials on the efficacy and safety of treatment with coenzyme Q10 compared to placebo in patients with early and midstage Parkinson's disease. We searched the Cochrane Movment Disorders Group Trials Register, CENTRAL (The Cochrane Library 2009, Issue 4), MEDLINE (January 1966 to March 2011), and EMBASE (January 1985 to March 2011). We handsearched the references quoted in the identified trials, congress reports from the most important neurological association and movement disorder societies in Europe and America (March 2011), checked reference lists of relevant studies and contacted other researchers. We included randomized controlled trials (RCTs) that compared coenzyme Q10 to placebo for patients who suffered early and midstage primary Parkinson's disease. Studies in which the method of randomization or concealment were unknown were included. Cross-over studies were excluded. Two review authors independently assessed trial quality and extracted data. All disagreements were resolved by consensus between authors and were explained. We attempted to contact the authors of studies for further details if any data were missing and to establish the characteristics of unpublished trials through correspondence with the trial coordinator or principal investigator. Adverse effects information was collected from the trials. Four randomized, double-blind, placebo-controlled trials with a total of 452 patients met the inclusion criteria and were included in the review. In overall, there were improvements in activities of daily living (ADL) UPDRS (WMD -3.12, 95% CI -5.88 to -0.36) and Schwab and England (WMD 4.43, 95% CI 0.05 to 8.81) for coenzyme Q10 at 1200 mg/d for 16 months versus placebo.In safety outcomes, only the risk ratios (RR) of pharyngitis (RR 1.04, 95% CI 0.18 to 5.89) and diarrhea (RR 1.39, 95% CI 0.62 to 3.16) are mild elevated between coenzyme Q10 therapy and placebo and there were no differences in the number of withdrawals due to adverse effects (RR 0.61, 95% CI 0.23 to 1.62). Coenzyme Q10 therapy with 1200 mg/d for 16 months was well tolerated by patients with Parkinson's disease. The improvements in ADL UPDRS and Schwab and England were positive, but it need to be further confirmed by larger sample. For total and other subscores of UPDRS, the effects of coenzyme Q10 seemed to be less clear.

Behavioral Improvement after Chronic Administration of Coenzyme Q10 in P301S Transgenic Mice

Coenzyme Q10 is a key component of the electron transport chain which plays an essential role in ATP production and also has antioxidant effects. Neuroprotective effects of coenzyme Q10 have been reported in both in vitro and in vivo models of neurodegenerative diseases. However, its effects have not been studied in cells or in animals with tau induced pathology. In this report, we administered coenzyme Q10 to transgenic mice with the P301S tau mutation, which causes fronto-temporal dementia in man. These mice develop tau hyperphosphorylation and neurofibrillary tangles in the brain. Coenzyme Q10 improved survival and behavioral deficits in the P301S mice. There was a modest reduction in phosphorylated tau in the cortex of P301S mice. We also examined the effects of coenzyme Q10 treatment on the electron transport chain enzymes, the mitochondrial antioxidant enzymes, and the tricarboxylic acid cycle. There was a significant increase in complex I activity and protein levels, and a reduction in lipid peroxidation. Our data show that coenzyme Q10 significantly improved behavioral deficits and survival in transgenic mice with the P301S tau mutation, upregulated key enzymes of the electron transport chain, and reduced oxidative stress.

Coenzyme Q10 protects neurons against neurotoxicity in hippocampal slice culture

This study investigated the neuroprotective effects of coenzyme Q10 (CoQ10) against oxidative stress induced by kainic acid (KA) in organotypic hippocampal slice culture of rats. Cultured slices were injured by exposure to 5 µM of KA for 18 h and then treated with different concentrations of CoQ10. Neuronal cell death measured as propidium iodide uptake was reduced at 24 h after treatment with 1 µM of CoQ10. We also observed an increased number of surviving CA3 neurons in 0.1 and 1 µM concentrations of CoQ10-treated groups using cresyl violet staining. CoQ10 (0.01, 0.1, and 1 µM) treatment significantly decreased the 2',7'-dichlorofluorescein fluorescence and the expression of NQO1 in the CoQ10-treated groups was significantly lower than that in the KA-only group. These results suggest that CoQ10 may protect hippocampal neurons against oxidative stress.

Neuroprotective effects of Coenzyme Q10 against beta-amyloid–induced neural stem cell death

Neuroprotective effects of Coenzyme Q10 against beta-amyloid–induced neural stem cell death

Neuroprotective effect of coenzyme Q10 at the striatal dopaminergic nerve terminal levels in MPTP-treated C57BL/6N mice

Neuroprotective effect of coenzyme Q10 at the striatal dopaminergic nerve terminal levels in MPTP-treated C57BL/6N mice

Neuroprotective effect of Coenzyme Q10 on ischemic hemisphere in aged mice with mutations in the amyloid precursor protein

This study was designed to test whether Coenzyme Q10 (CoQ10) supplementation has neuroprotective effect in aged, double-transgenic amyloid precursor protein (APP)/presenilin 1 (PS1), single transgenic APP and PS1 mice exposed to ischemic injury of the brain. Forty-eight mice (12 each of APP/PS1, APP, PS1 and wild-type) were studied. Half of each genotype groups (n=6 per group) was treated with CoQ10 (1200mg/kg/day) after ischemic injury and the other half with placebo. Magnetic resonance (MR) images were used to measure the volume of induced infarction (IFV), as well as the volume of the hemispheres and hippocampi. Significantly greater volumes of infarction and lesser volumes of hemisphere/hippocampus on the ischemic side were observed in APP/PS1 and APP mice than in PS1 and wild-type mice. This is consistent with amplification of the effect of ischemia in APP carriers. After 28 days of CoQ10 treatment, APP/PS1 or APP mutations have smaller infarct volumes, while the volumes of hemisphere and hippocampus on the infarcted side were larger than those treated with placebo. No differences between CoQ10- and placebo-treated groups in volumes of infarct, hemisphere and hippocampus were observed in PS1 and wild-type mice. We conclude that CoQ10 has a protective effect on the brain from infarction and atrophy induced by ischemic injury in aged and susceptible transgenic mice.

Coenzyme Q10 protects SHSY5Y neuronal cells from beta amyloid toxicity and oxygen‐glucose deprivation by inhibiting the opening of the mitochondrial permeability transition pore

Coenzyme Q10 (CoQ10) is an essential biological cofactor which increases brain mitochondrial concentration and exerts neuroprotective effects. In the present study, we exposed SHSY5Y neuroblastoma cells to neurotoxic beta amyloid peptides (Abeta) and oxygen glucose deprivation (OGD) to investigate the neuroprotective effect of 10 microM CoQ10 by measuring (i) cell viability by the MTT assay, (ii) opening of the mitochondrial permeability transition pore via the fluorescence intensity of calcein-AM, and (iii) superoxide anion concentration by hydroethidine. Cell viability (mean +/- S.E.M.) was 55.5 +/- 0.8% in the group exposed to Abeta + OGD, a value lower than that in the Abeta or OGD group alone (P < 0.01). CoQ10 had no neuroprotective effect on cell death induced by either Abeta or OGD, but increased cell survival in the Abeta + OGD group to 57.3 +/- 1.7%, which was higher than in the group treated with vehicle (P < 0.05). The neuroprotective effect of CoQ10 was blocked by administration of 20 microM atractyloside. Pore opening and superoxide anion concentration were increased in the Abeta + OGD group relative to sham control (P < 0.01), and were attenuated to the sham level (P > 0.05) when CoQ10 was administered. Our results demonstrate that CoQ10 protects neuronal cells against Abeta neurotoxicity together with OGD by inhibiting the opening of the pore and reducing the concentration of superoxide anion.

Neuroprotective effects of coenzyme Q10 at rostral ventrolateral medulla against fatality during experimental endotoxemia in the rat.

Coenzyme Q10 (CoQ10, ubiquinone) is a highly mobile electron carrier in the mitochondrial respiratory chain that also acts as an antioxidant. We evaluated the neuroprotective efficacy of CoQ10 against fatality in an experimental model of endotoxemia that mimics systemic inflammatory response syndrome using a novel water-soluble formulation of this quinone derivative. Experiments were conducted in adult male Sprague-Dawley rats that were maintained under propofol anesthesia. Intravenous administration of Escherichia coli lipopolysaccharide (LPS; 30 mg/kg) induced progressive hypotension, with death ensuing within 4 h. The sequence of cardiovascular events during this LPS-induced endotoxemia can be divided into a reduction (Phase I), followed by an augmentation (Phase II; "pro-life" phase) and a secondary decrease (Phase III; "pro-death" phase) in the power density of the vasomotor components (0-0.8 Hz) of systemic arterial pressure signals. Pretreatment by microinjection bilaterally of CoQ10 (1 or 2 microg) into the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor tone, significantly diminished mortality, prolonged survival time, and reduced the slope or magnitude of the LPS-induced hypotension. CoQ10 pretreatment also significantly prolonged the duration of and augmented the total power density of the vasomotor components of systemic arterial pressure signals in Phase II endotoxemia. The increase in superoxide anion production induced by LPS at the RVLM during Phases II and III endotoxemia was also significantly blunted. We conclude that CoQ10 provides neuroprotection against fatality during experimental endotoxemia by reducing superoxide anion production at the RVLM, whose neuronal activity is intimately related to the "life-and-death" process.