Show simple item record

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.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.relation.isformatofVersió postprint del document publicat a:
dc.relation.ispartofNeuropharmacology, 2019, vol. 146, p. 184-197
dc.rightscc-by-nc-nd, (c) Elsevier, 2019
dc.titleOleoylethanolamide restores alcohol-induced inhibition of neuronal proliferation and microglial activity in striatum

Files in this item


This item appears in the following Collection(s)

Show simple item record

cc-by-nc-nd, (c) Elsevier, 2019
Except where otherwise noted, this item's license is described as cc-by-nc-nd, (c) Elsevier, 2019