Line Berthiaume

Publications (5)16.79 Total impact

• Article: High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model.

  Carl Julien, Cyntia Tremblay, Alix Phivilay, Line Berthiaume, Vincent Emond, Pierre Julien, Frédéric Calon
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  ABSTRACT: To investigate potential dietary risk factors of Alzheimer's disease (AD), triple transgenic (3xTg-AD) mice were exposed from 4 to 13 months of age to diets with a low n-3:n-6 polyunsaturated fatty acid (PUFA) ratio incorporated in either low-fat (5% w/w) or high-fat (35% w/w) formulas and compared with a control diet. The n-3:n-6 PUFA ratio was decreased independently of the dietary treatments in the frontal cortex of 3xTg-AD mice compared to non-transgenic littermates. Consumption of a high-fat diet with a low n-3:n-6 PUFA ratio increased amyloid-beta (Abeta) 40 and 42 concentrations in detergent-insoluble extracts of parieto-temporal cortex homogenates from 3xTg-AD mice. Low n-3:n-6 PUFA intake ratio increased insoluble tau regardless of total fat consumption, whereas high-fat diet incorporating a low n-3:n-6 PUFA ratio also increased soluble tau compared to controls. Moreover, the high-fat diet decreased cortical levels of the postsynaptic marker drebrin, while leaving presynaptic proteins synaptophysin, SNAP-25 and syntaxin 3 unchanged. Overall, these results suggest that high-fat consumption combined with low n-3 PUFA intake promote AD-like neuropathology.
  Neurobiology of aging 11/2008; 31(9):1516-31. · 5.94 Impact Factor
• Article: Environmental contaminants and redox status of coenzyme Q10 and vitamin E in Inuit from Nunavik.

  Marie-Claire Bélanger, Marc-Edouard Mirault, Eric Dewailly, Line Berthiaume, Pierre Julien
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  ABSTRACT: The Inuit are heavily exposed to potentially prooxidant contaminants such as methylmercury (MeHg) and polychlorinated biphenyls (PCB) through their traditional diet. This diet is also an abundant source of n-3 polyunsaturated fatty acids (n-3 PUFA), selenium, and antioxidants, which might reduce cardiovascular risk. Although Inuit from Nunavik have low concentrations of plasma oxidized low-density lipoprotein (OxLDL) and elevated glutathione-related antioxidant defenses, the variance in OxLDL was predicted by PCB and blood glutathione, leaving the issue of contaminant-associated oxidative stress unresolved. The objective of the study was to assess oxidative stress in these Inuit by measuring the plasma concentrations and redox states of alpha-tocopherol and coenzyme Q10 (CoQ10), 2 sensitive biomarkers of oxidative stress, in relation to exposure. Plasma lipophilic antioxidants were determined by high-performance liquid chromatography-coupled electrochemical detection; and their relations to PCB, MeHg, n-3 PUFA, selenium, and OxLDL were assessed by multivariate analyses. Ubiquinol-10, ubiquinone-10, and ubiquinone-10 to CoQ10(total) ratio were elevated as compared with white populations but showed no associations with PCB, MeHg, or n-3 PUFA. Ubiquinol-10 (beta = .23, P = .007) and CoQ10(total) (beta = .27, P = .009) were predicted by blood selenium; and alpha-tocopherol, by PCB (beta = 4.12, P = .0002), n-3 PUFA (beta = 9.16, P = .02), and OxLDL (beta = 3.04, P = .05). Unexpectedly, the alpha-tocopheryl quinone to alpha-tocopherol ratio, in the reference range, was negatively predicted by PCB (beta = -0.41, P = .02). Using sensitive biomarkers of redox alterations, we found no evidence for MeHg- or PCB-associated oxidative stress in these Inuit. However, despite robust blood antioxidant defenses, the unusually elevated ubiquinone-10 to CoQ10(total) ratio (0.21 +/- 0.11) suggests some form of oxidative stress of unknown origin.
  Metabolism 08/2008; 57(7):927-33. · 2.66 Impact Factor
• Article: Seasonal mercury exposure and oxidant-antioxidant status of James Bay sport fishermen.

  Marie-Claire Bélanger, Marc-Edouard Mirault, Eric Dewailly, Michel Plante, Line Berthiaume, Micheline Noël, Pierre Julien
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  ABSTRACT: The effects of a moderate seasonal exposure to methylmercury on plasma low-density lipoprotein (LDL) oxidation and cardiovascular risk indices are not known. The objective of the study was to assess the effects of a seasonal exposure to mercury at similar dose reported to increase cardiovascular risk through fish consumption. Effects on lipoprotein cholesterol and fatty acid profiles, LDL oxidation, and blood oxidant-antioxidant balance were to be assessed in sport fishermen presenting normal blood selenium and omega-3 fatty acid contents. Thirty-one healthy James Bay sport fishermen were assessed for within-subject longitudinal seasonal variations in hair and blood mercury, plasma oxidized LDL, lipophilic antioxidants, homocysteine, blood selenium, and glutathione peroxidase and reductase activities determined before and after the fishing season and compared by matched-pair tests. Hair mercury doubled during the fishing season (2.8+/-0.4 microg/g, P<.0001). Baseline blood selenium, homocysteine, and erythrocyte fatty acid profiles did not change. Plasma high-density lipoprotein cholesterol increased (+5%, P=.05), whereas very low-density lipoprotein cholesterol and oxidized LDL decreased (-8%, P=.05; -18%, P=.008). Blood glutathione peroxidase (+9.7%, P=.001), glutathione reductase (+7.2%, P<.0001), and total glutathione (+45% P<.0001) increased during the fishing season. Plasma total coenzyme Q10 (+13%, P=.02), ubiquinone-10 (+67%, P=.03), and beta-carotene (+46%, P=.01) also increased, whereas vitamin E status was unaffected. Pairwise correlations revealed no association between mercury exposure and any of the biomarkers investigated. In contrast, strong predictors of cardiovascular risk such as high-density lipoprotein cholesterol, oxidized LDL, and glutathione peroxidase improved during the fishing season despite elevated methylmercury exposure. The beneficial effects of seasonal fishing activity and fish consumption on cardiovascular health may suppress detrimental effects of concomitant moderate methylmercury exposure.
  Metabolism 06/2008; 57(5):630-6. · 2.66 Impact Factor
• Article: Dietary contaminants and oxidative stress in Inuit of Nunavik.

  Marie-Claire Bélanger, Eric Dewailly, Line Berthiaume, Micheline Noël, Jean Bergeron, Marc-Edouard Mirault, Pierre Julien
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  ABSTRACT: The aim of the present study was to investigate the potential deleterious effects of dietary contaminants such as polychlorinated biphenyls (PCBs) and methylmercury (MeHg) on different molecules sensitive to oxidative stress, namely, plasma oxidized low-density lipoproteins (OxLDLs), plasma homocysteine (Hcy), blood glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH). We also planned to assess the potential beneficial effects of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) and selenium (Se) that are also present in the traditional Inuit diet. A total of 99 participants were studied. Plasma levels of PCBs, blood levels of Se and MeHg, plasma lipids (triacylglycerols, total, LDL-, and high-density lipoprotein cholesterol [LDL-C and HDL-C, respectively], apolipoprotein B-LDL), erythrocyte n-3 PUFAs, OxLDL, Hcy, blood GPx, GSH, and GR have been determined. Mean concentrations of MeHg, Se, and PCBs were respectively 10- to 14-fold, 8- to 15-fold, and 16- to 18-fold higher than reported in white population consuming little or no fish. Multivariate analyses show that variance in plasma OxLDL concentrations was predicted by LDL-C (P = .007), HDL-C (P = .005), and PCBs (P = .006). The level of LDL oxidation, represented as the ratio OxLDL/apolipoprotein B-LDL, was predicted by LDL-C (P = .0002), HDL-C (P = .002), and GSH (P = .005). Concentration of plasma Hcy was positively predicted by age (P = .02) but negatively by body mass index (P = .04) and Se (P = .005). Glutathione was predicted by the smoking status (P = .004) and the level of LDL oxidation (P = .005), whereas GR was only predicted by the smoking status (P = .0009). The variance of GPx was not predicted by any contaminant or other physiological parameter. Dietary MeHg showed no association with the examined oxidative biomarkers, whereas PCB level was a predictor of the plasma concentration of OxLDL, although this concentration remained very low. The level of GPx activity in Inuit was higher than levels previously reported to be protective in whites. Homocysteine was negatively predicted by Se, suggesting a possible beneficial effect of Se. Moreover, n-3 PUFAs were highly correlated with dietary contaminants, but had no relationships with oxidative biomarkers. This study suggests that, in adult Inuit, contaminated traditional diet seems to have no direct oxidative effects on molecules involved in oxidative stress.
  Metabolism 09/2006; 55(8):989-95. · 2.66 Impact Factor
• Article: Postmortem brain fatty acid profile of levodopa-treated Parkinson disease patients and parkinsonian monkeys.

  Carl Julien, Line Berthiaume, Abdallah Hadj-Tahar, Ali H Rajput, Paul J Bédard, Thérèse Di Paolo, Pierre Julien, Frédéric Calon
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  ABSTRACT: Fatty acids play a critical role in brain function but their specific role in the pathophysiology of Parkinson disease (PD) and levodopa-induced motor complications is still unknown. From a therapeutic standpoint, it is important to determine the relation between brain fatty acids and PD because the brain fatty acid content depends on nutritional intake, a readily manipulable environmental factor. Here, we report a postmortem analysis of fatty acid profile by gas chromatography in the brain cortex of human patients (12 PD patients and nine Controls) as well as in the brain cortex of monkeys (four controls, five drug-naive MPTP monkeys and seven levodopa-treated MPTP monkeys). Brain fatty acid profile of cerebral cortex tissue was similar between PD patients and Controls and was not correlated with age of death, delay to autopsy or brain pH. Levodopa administration in MPTP monkeys increased arachidonic acid content (+7%; P < 0 .05) but decreased docosahexaenoic acid concentration (-15%; P < 0.05) and total n-3:n-6 polyunsaturated fatty acids ratio (-27%; P < 0.01) compared to drug-naive MPTP animals. Interestingly, PD patients who experienced motor complications to levodopa had higher arachidonic acid concentrations in the cortex compared to Controls (+13.6%; P < 0.05) and to levodopa-treated PD patients devoid of motor complications (+14.4%; P < 0.05). Furthermore, PD patients who took an above-median cumulative dose of levodopa had a higher relative amount of saturated fatty acids but lower monounsaturated fatty acids in their brain cortex (P < 0.01). These results suggest that changes in brain fatty acid relative concentrations are associated with levodopa treatment in PD patients and in a non-human primate model of parkinsonism.
  Neurochemistry International 04/2006; 48(5):404-14. · 2.86 Impact Factor