Oleoylethanolamide restores alcohol-induced inhibition of neuronal proliferation and microglial activity in striatum

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dc.contributor.authorRivera, Patricia
dc.contributor.authorSilva Peña, Daniel
dc.contributor.authorBlanco Calvo, Eduardo
dc.contributor.authorVargas, Antonio
dc.contributor.authorArrabal, Sergio
dc.contributor.authorSerrano, Antonia
dc.contributor.authorPavón, Francisco Javier
dc.contributor.authorBindila, Laura
dc.contributor.authorLutz, Beat
dc.contributor.authorRodríguez de Fonseca, Fernando
dc.contributor.authorSuárez, Juan
dc.date.accessioned2020-01-14T09:28:10Z
dc.date.available2020-03-01T23:18:19Z
dc.date.issued2019-03-01
dc.date.updated2020-01-14T09:28:10Z
dc.description.abstractPrevious findings demonstrate a homeostatic role for oleoylethanolamide (OEA) signaling in the ethanol-related neuroinflammation and behavior. However, extensive research is still required in order to unveil the effects of OEA on a number of neurobiological functions such as adult neurogenesis, cell survival and resident neuroimmunity that become notably altered by alcohol. Daily consumption of ethanol (10%) for 2 weeks (6.3& #x202F;± 1.1 g/kg/day during last 5 days) caused hypolocomotor activity in rats. This effect appears to rely on central signaling mechanisms given that alcohol increased the OEA levels, the gene expression of OEA-synthesizing enzyme Nape-pld and the number of PPARα-immunoreactive neurons in the striatum. Ethanol-related neurobiological alterations such as a reduction in the number of microglial cells expressing iNOS (a cytokine-inducible immune defense) and in adult neural stem/progenitor cell (NSPC) proliferation (phospho-H3 and BrdU) and maturation (BrdU/β3-tubulin), as well as an increase in damage cell activity (FosB) and apoptosis (cleaved caspase 3) were also observed in the rat striatum. Pharmacological administration of OEA (10 mg/kg) for 5 days during ethanol exposure exacerbated ethanol-induced hypolocomotion and cell apoptosis in the striatum. Interestingly, OEA abrogated the impaired effects of ethanol on PPARα-positive cell population and NSPC proliferation and maturation. OEA also decreased astrocyte-related vimentin immunoreactivity and increased microglial cell population (Iba-1, iNOS) in the striatum. These results suggest that OEA-PPARα signaling modulates glial activation, cell apoptosis and NSPC proliferation and maturation in response to striatal-specific neurobiological alterations induced by prolonged ethanol intake in rats.
dc.description.sponsorshipThis work was supported by RETICS Red de Trastornos Adictivos, Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad and European Regional Development Funds-European Union (ERDF-EU) (RD16/0017/0001); ISCIII, MINECO, ERDF-EU (JS: PI16/01374; FRF: PI16/01698; FJP: PI16/01953; AS: PI17/02026); Ministerio de Sanidad, Servicios Sociales e Igualdad and Plan Nacional sobre Drogas (JS: PNSD2015/047; AS: PND2017/043); Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, ERDF-EU (FRF: CTS-8221); Consejería de Salud, Junta de Andalucía, ERDF-EU (FRF: SAS111224); German Research Foundation DFG (BL: FOR926, project CP1). FJP (CP14/00212) and AS (CP14/00173) are recipients of a research contract from “Miguel Servet” Program of ISCIII, ERDF-EU. JS holds a “Miguel Servet II” research contract from the National System of Health, ISCIII, ERDF-EU, FIMABIS (CPII17/00024). PR holds a “Sara Borrel” research contract from ISCIII, ERDF-EU (CD16/00067).
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1016/j.neuropharm.2018.11.037
dc.identifier.idgrec029329
dc.identifier.issn0028-3908
dc.identifier.urihttp://hdl.handle.net/10459.1/67806
dc.language.isoeng
dc.publisherElsevier
dc.relation.isformatofVersió postprint del document publicat a: https://doi.org/10.1016/j.neuropharm.2018.11.037
dc.relation.ispartofNeuropharmacology, 2019, vol. 146, p. 184-197
dc.rightscc-by-nc-nd, (c) Elsevier, 2019
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAlcohol
dc.subjectPPARα
dc.titleOleoylethanolamide restores alcohol-induced inhibition of neuronal proliferation and microglial activity in striatum
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
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