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

NEUROPHARMACOLOGY

卷:146

Article

Rivera, Patricia¹  Silva-Pena, Daniel²  Blanco, Eduardo³  Vargas, Antonio²  Arrabal, Sergio²  Serrano, Antonia²  Javier Pavon, Francisco²  Bindila, Laura⁴  Lutz, Beat⁴  Rodriguez de Fonseca, Fernando²  Suarez, Juan² 

[1] Hosp Infantil Univ Nino Jesus, Dept Endocrinol, Fdn Invest Biomed, Madrid, Spain

[2] Univ Malaga, Inst Invest Biomed Malaga IBIMA, Hosp Univ Reg Malaga, UGC Salud Mental, Malaga, Spain

[3] Univ Lleida, Inst Biomed Res Lleida IRB Lleida, Lleida, Spain

[4] Johannes Gutenberg Univ Mainz, Univ Med Ctr, German Resilience Ctr DRZ, Inst Physiol Chem, Mainz, Germany

关键词: Alcohol;    PPAR alpha;    Microglia;    Neurogenesis;    Locomotion;    Striatum;   

DOI  :  10.1016/j.neuropharm.2018.11.037

来源: Elsevier

【 摘 要 】

Previous 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 PPAR alpha-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/beta 3-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 hypoloco-motion and cell apoptosis in the striatum. Interestingly, OEA abrogated the impaired effects of ethanol on PPAR alpha-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-PPAR alpha 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.

【 授权许可】

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