In vitro effect of quinolinic acid on energy metabolism in brain of young rats

Schuck, Patrícia Fernanda; Tonin, Anelise Miotti; Ferreira, Gustavo da Costa; Rosa, Ricardo Abreu da; Latini, Alexandra; Balestro, Fabrício; Perry, Marcos Luiz Santos; Wannmacher, Clóvis Milton Duval; Wyse, Ângela T. S.; Wajner, Moaçir

doi:10.1016/j.neures.2006.10.013

Cited by 26 publications

(17 citation statements)

References 78 publications

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“…In contrast, little is known about the effect of QA on brain energy metabolism. In this context, previous investigators have shown that intrastriatal injection of QA provoke a decrease in cellular respiration and ATP levels [40].…”

Section: Discussionmentioning

confidence: 97%

Neurodegeneration Alters Metabolic Profile and Sirt 1 Signaling in High-Fat-Induced Obese Mice

et al. 2016

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Different factors may contribute to the development of neurodegenerative diseases. Among them, metabolic syndrome (MS), which has reached epidemic proportions, has emerged as a potential element that may be involved in neurodegeneration. Furthermore, studies have shown the importance of the sirtuin family in neuronal survival and MS, which opens the possibility of new pharmacological targets. This study investigates the influence of sirtuin metabolic pathways by examining the functional capacities of glucose-induced obesity in an excitotoxic state induced by a quinolinic acid (QA) animal model. Mice were divided into two groups that received different diets for 8 weeks: one group received a regular diet, and the other group received a high-fat diet (HF) to induce MS. The animals were submitted to a stereotaxic surgery and subdivided into four groups: Standard (ST), Standard-QA (ST-QA), HF and HF-QA. The QA groups were given a 250 nL quinolinic acid injection in the right striatum and PBS was injected in the other groups. Obese mice presented with a weight gain of 40 % more than the ST group beyond acquiring an insulin resistance. QA induced motor impairment and neurodegeneration in both ST-QA and HF-QA, although no difference was observed between these groups. The HF-QA group showed a reduction in adiposity when compared with the groups that received PBS. Therefore, the HF-QA group demonstrated a commitment-dependent metabolic pathway. The results suggest that an obesogenic diet does not aggravate the neurodegeneration induced by QA. However, the excitotoxicity induced by QA promotes a sirtuin pathway impairment that contributes to metabolic changes.

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Section: Discussionmentioning

confidence: 97%

Neurodegeneration Alters Metabolic Profile and Sirt 1 Signaling in High-Fat-Induced Obese Mice

et al. 2016

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“…(Guidetti and Schwarcz 2003). Interestingly, abnormal energy metabolism has been demonstrated in postmortem HD brain, most notably reduced activity of succinatelinked oxidation and activities of the respiratory chain complexes (Schuck et al 2007). Although QA-induced excitotoxicity and free radical generation have been extensively studied as mechanisms of neural cell damage, few studies examined the role of QA on mitochondrial enzyme complex.…”

Section: Discussionmentioning

confidence: 99%

“…The present study showed that QA significantly impaired mitochondrial enzyme complex-I, -II, -IV activities and redox activity in the ex vivo striatum suggesting its role in mitochondrial dysfunction in QA-induced neurotoxicity (Arenas et al 1998). Previous investigators have suggested that intrastriatal injection of QA reduce CO 2 production, and further inhibit citric acid cycle and/or the respiratory chain, that block aerobic metabolism (Schuck et al 2007). QA specifically inhibits complex-II enzyme in mitochondrial preparations, since it is largely demonstrated that QA is able to induce reactive species formation (Behan et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Effect of caffeic acid and rofecoxib and their combination against intrastriatal quinolinic acid induced oxidative damage, mitochondrial and histological alterations in rats

Kalonia

Kumar

et al. 2009

Inflammopharmacol

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Oxidative stress has long been implicated in the neurotoxic effects of glutamate acting through N-methyl-D-aspartate (NMDA) receptors. Therefore, present study has been designed to explore the effect of rofecoxib and caffeic acid on the involvement of oxidative stress, mitochondrial dysfunction and neuronal linked with NMDA receptor-mediated excitotoxicity. Caffeic acid, is a well-known antioxidant flavanoid, implicate anti-inflammatory and immunomodulatory like actions. The present study is an attempt to investigate the antioxidant-like effect of caffeic acid and rofecoxib and their combination against QA-induced oxidative damage, mitochondrial dysfunction and histological alterations. Intrastriatal injection of quinolinic acid (300 nmol) significantly increased oxidative stress (raised lipid peroxidation, nitrite concentration, depleted SOD and catalase), altered mitochondrial complex enzyme activities and histological alteration in the ex vivo striatum. Caffeic acid (5 and 10 mg/kg, p.o.) and rofecoxib (10 and 20 mg/kg, p.o.) treatment for 21 days significantly attenuated oxidative damage and impairment in mitochondrial activities of complex enzymes in the ex vivo striatum. Further, combination of sub effective doses of rofecoxib (10 mg/kg, p.o.) and caffeic acid (5 mg/kg, p.o.) potentiated their protective effect which was significant as compared to their effect per se. The present study suggests the therapeutic effect of caffeic acid and rofecoxib combination against QA-induced ex vivo oxidative damage, mitochondrial and histological alterations in rats.

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“…Disrupted mitochondrial fractions were obtained by freezing/thawing the samples three times. The NADH dehydrogenase (complex I), succinate dehydrogenase (complex II) and cytochrome c oxidase (complex IV) activities were analyzed [85] with the plate reader Infinite™ M200 (TECAN, Männedorf, Switzerland). The activities of the respiratory chain complexes are calculated as nmol min −1 /mg protein −1 or mmol min −1 /mg protein −1 ± S.E.M.…”

Section: Methodsmentioning

confidence: 99%

In Vivo Manganese Exposure Modulates Erk, Akt and Darpp-32 in the Striatum of Developing Rats, and Impairs Their Motor Function

et al. 2012

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Manganese (Mn) is an essential metal for development and metabolism. However, exposures to high Mn levels may be toxic, especially to the central nervous system (CNS). Neurotoxicity is commonly due to occupational or environmental exposures leading to Mn accumulation in the basal ganglia and a Parkinsonian-like disorder. Younger individuals are more susceptible to Mn toxicity. Moreover, early exposure may represent a risk factor for the development of neurodegenerative diseases later in life. The present study was undertaken to investigate the developmental neurotoxicity in an in vivo model of immature rats exposed to Mn (5, 10 and 20 mg/kg; i.p.) from postnatal day 8 (PN8) to PN12. Neurochemical analysis was carried out on PN14. We focused on striatal alterations in intracellular signaling pathways, oxidative stress and cell death. Moreover, motor alterations as a result of early Mn exposure (PN8-12) were evaluated later in life at 3-, 4- and 5-weeks-of-age. Mn altered in a dose-dependent manner the activity of key cell signaling elements. Specifically, Mn increased the phosphorylation of DARPP-32-Thr-34, ERK1/2 and AKT. Additionally, Mn increased reactive oxygen species (ROS) production and caspase activity, and altered mitochondrial respiratory chain complexes I and II activities. Mn (10 and 20 mg/kg) also impaired motor coordination in the 3 rd , 4 th and 5 th week of life. Trolox™, an antioxidant, reversed several of the Mn altered parameters, including the increased ROS production and ERK1/2 phosphorylation. However, Trolox™ failed to reverse the Mn (20 mg/kg)-induced increase in AKT phosphorylation and motor deficits. Additionally, Mn (20 mg/kg) decreased the distance, speed and grooming frequency in an open field test; Trolox™ blocked only the decrease of grooming frequency. Taken together, these results establish that short-term exposure to Mn during a specific developmental window (PN8-12) induces metabolic and neurochemical alterations in the striatum that may modulate later-life behavioral changes. Furthermore, some of the molecular and behavioral events, which are perturbed by early Mn exposure are not directly related to the production of oxidative stress.

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In vitro effect of quinolinic acid on energy metabolism in brain of young rats

Cited by 26 publications

References 78 publications

Neurodegeneration Alters Metabolic Profile and Sirt 1 Signaling in High-Fat-Induced Obese Mice

Neurodegeneration Alters Metabolic Profile and Sirt 1 Signaling in High-Fat-Induced Obese Mice

Effect of caffeic acid and rofecoxib and their combination against intrastriatal quinolinic acid induced oxidative damage, mitochondrial and histological alterations in rats

In Vivo Manganese Exposure Modulates Erk, Akt and Darpp-32 in the Striatum of Developing Rats, and Impairs Their Motor Function

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