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Differential effects of cocaine exposure on the abundance of phospholipid species in rat brain and blood.

ABSTRACT: Lipid profiles in the blood are altered in human cocaine users, suggesting that cocaine exposure can induce lipid remodeling.Lipid changes in the brain tissues of rats sensitized to cocaine were determined through shotgun lipidomics using electrospray ionization-mass spectrometry (ESI-MS). We also performed pairwise principal component analysis (PCA) to assess cocaine-induced changes in blood lipid profiles. Alterations in the abundance of phospholipid species were correlated with behavioral changes in the magnitude of either the initial response to the drug or locomotor sensitization.Behavioral sensitization altered the relative abundance of several phospholipid species in the hippocampus and cerebellum, measured one week following the final exposure to cocaine. In contrast, relatively few effects on phospholipids in either the dorsal or the ventral striatum were observed. PCA analysis demonstrated that cocaine altered the relative abundance of several glycerophospholipid species as compared to saline-injected controls in blood. Subsequent MS/MS analysis identified some of these lipids as phosphatidylethanolamines, phosphatidylserines and phosphatidylcholines. The relative abundance of some of these phospholipid species were well-correlated (R(2) of 0.7 or higher) with either the initial response to cocaine or locomotor sensitization.Taken together, these data demonstrate that a cocaine-induced sensitization assay results in the remodeling of specific phospholipids in rat brain tissue in a region-specific manner and also alters the intensities of certain types of phospholipid species in rat blood. These results further suggest that such changes may serve as biomarkers to assess the neuroadaptations occurring following repeated exposure to cocaine.

SUBMITTER: Cummings BS

PROVIDER: S-EPMC4458179 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Differential effects of cocaine exposure on the abundance of phospholipid species in rat brain and blood.

Cummings Brian S BS Pati Sumitra S Sahin Serap S Scholpa Natalie E NE Monian Prashant P Trinquero Paul M PM Clark Jason K JK Wagner John J JJ

Drug and alcohol dependence 20150422

<h4>Background</h4>Lipid profiles in the blood are altered in human cocaine users, suggesting that cocaine exposure can induce lipid remodeling.<h4>Methods</h4>Lipid changes in the brain tissues of rats sensitized to cocaine were determined through shotgun lipidomics using electrospray ionization-mass spectrometry (ESI-MS). We also performed pairwise principal component analysis (PCA) to assess cocaine-induced changes in blood lipid profiles. Alterations in the abundance of phospholipid species ...[more]

PMID: 25960140

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Project description:BackgroundHydrogen sulfide (H2S), as the third gasotransmitter participates in both cellular physiological and pathological processes, including chemical-induced injuries. We recently reported acute acrylonitrile (AN) treatment inhibited endogenous H2S biosynthesis pathway in rat and astrocyte models. However, there is still no evidence to address the correlation between endogenous H2S and sub-chronic AN exposure.ObjectivesThis study aims to explore the modulatory effects of prolonged AN exposure on endogenous H2S levels and its biosynthetic enzymes in rat blood, brain and liver.MethodsA total of 50 male Sprague-Dawley rats were randomly divided into 5 groups, including the control group and AN-treated groups at dosages of 6.25, 12.5, 25 or 50 mg/kg. Rats received one exposure/day, 5 days/week, for 4 consecutive weeks. The rat bodyweight and brain/liver organ coefficient were detected, along with liver cytochrome P450 2E1(CYP2E1) expression. In addition, the H2S contents in rat serum and plasma, and in cerebral cortex and liver tissues were measured by methylene blue method. The expression of H2S-generating enzymes, including cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MPST) was also measured with Western blot both in rat cerebral cortex and liver.ResultsSubchronic exposure to AN significantly inhibited bodyweight-gain and increased the liver CYP2E1 expression compared with the control. In addition, AN significantly increased H2S levels in rat plasma and serum, but not in liver. The endogenous H2S level in rat cerebral cortex was also significantly increased upon AN treatment, when expression of the major H2S-generating enzymes, CBS and 3-MPST were significantly enhanced. However, hepatic protein levels of CBS and CSE were significantly increased, whereas hepatic levels of 3-MPST were significantly decreased.ConclusionThis study showed that sub-chronic AN exposure increased endogenous H2S contents in rat blood and brain tissues, but not liver, which may be resulted from the distinct expression profile of H2S-producing enzymes in response to AN. The blood H2S contents may be applied as a potential novel biomarker for surveillance of chronically AN-exposed populations.HighlightsSubchronic intraperitoneal exposure to acrylonitrile increased H2S content in rat blood and cerebral cortex, but not in liver.Distinct tissue expression profiles of H2S-producing enzymes contribute to the acrylonitrile-induced differential effects on the H2S level.Blood H2S level may be a biomarker for subchronic exposure to acrylonitrile.

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Differential effects of cocaine exposure on the abundance of phospholipid species in rat brain and blood.

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Differential effects of cocaine exposure on the abundance of phospholipid species in rat brain and blood.

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