Effect of antidepressant drugs on the brain sphingolipid system

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dc.cclicenceCC-BY-NCen
dc.contributor.authorZetterstrom, Tyra
dc.contributor.authorJaddoa, Estabraq
dc.contributor.authorMasania, Jinit
dc.contributor.authorMasiero, Eva
dc.contributor.authorSgamma, Tiziana
dc.contributor.authorArroo, R. R. J.
dc.contributor.authorSillence, Daniel J.
dc.date.acceptance2020-03-02
dc.date.accessioned2020-03-26T11:48:43Z
dc.date.available2020-03-26T11:48:43Z
dc.date.issued2020-05-14
dc.descriptionThe file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.en
dc.description.abstractBackground: Major depression is a common mood disorder and the central sphingolipid system has been identified as a possible drug target of this condition. Here we investigated the action of antidepressant drugs on sphingolipid levels in rat brain regions, plasma and in cultured mouse macrophages. Methods: Two antidepressant drugs were tested; the serotonin reuptake inhibitor paroxetine and the noradrenaline reuptake inhibitor desipramine, either following acute or chronic treatments. Content of sphingosine and ceramide were analysed using LC-MS or HPLC-UV respectively. This from samples of brain, plasma and cultured mouse macrophages. Antidepressant induced effects on mRNA expression for two key genes of the sphingolipid pathway, SMPD1 and ASAH1 were also measured by using quantitative Real-Time PCR. Results: Chronic but not acute administration of paroxetine or desipramine reduced sphingosine levels in the prefrontal cortex and hippocampus (only paroxetine) but not in the striatum. Ceramide levels were also measured in the hippocampus following chronic paroxetine and likewise to sphingosine this treatment reduced its levels. The corresponding collected plasma samples from chronically treated animals did not show any decrease of sphingosine compared to the corresponding controls. Both drugs failed to reduce sphingosine levels from cultured mouse macrophages. The drug-induced decrease of sphingolipids coincided with reduced mRNA expression of two enzymes of the central sphingolipid pathway, i.e. acid sphingomyelinase (SMPD1) and acid ceramidase (ASAH1). Conclusions: This study supports the involvement of brain sphingolipids in the mechanism of action by antidepressant drugs and for the first time highlights their differential effects on brain versus plasma levels.en
dc.funderNo external funderen
dc.identifier.citationJaddoa, E. et al. (2020) Effect of antidepressant drugs on the brain sphingolipid system. Journal of Psychopharmacology, 34 (7), pp. 716-725en
dc.identifier.doihttps://doi.org/10.1177/0269881120915412
dc.identifier.urihttps://dora.dmu.ac.uk/handle/2086/19456
dc.language.isoenen
dc.peerreviewedYesen
dc.publisherSage
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en
dc.subjectParoxetine, Desipramine, Drugs for depression, Ceramide, Sphingosine, Acid sphingomyelinase, Acid ceramidaseen
dc.subjectNeuropharmacologyen
dc.subjectNeuroscienceen
dc.subjectPsychopharmacologyen
dc.subjectParoxetineen
dc.subjectDesipramineen
dc.subjectDrugs for depressionen
dc.subjectCeramideen
dc.subjectSphingosineen
dc.subjectAcid sphingomyelinaseen
dc.subjectAcid ceramidaseen
dc.titleEffect of antidepressant drugs on the brain sphingolipid systemen
dc.typeArticleen

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