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

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2019-03-01Author
Rivera, Patricia
Silva Peña, Daniel
Vargas, Antonio
Arrabal, Sergio
Serrano, Antonia
Pavón, Francisco Javier
Bindila, Laura
Lutz, Beat
Rodríguez de Fonseca, Fernando
Suárez, Juan
Suggested citation
Rivera, Patricia;
Silva Peña, Daniel;
Blanco Calvo, Eduardo;
Vargas, Antonio;
Arrabal, Sergio;
Serrano, Antonia;
...
Suárez, Juan.
(2019)
.
Oleoylethanolamide restores alcohol-induced inhibition of neuronal proliferation and microglial activity in striatum.
Neuropharmacology, 2019, vol. 146, p. 184-197.
https://doi.org/10.1016/j.neuropharm.2018.11.037.
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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 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.
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Neuropharmacology, 2019, vol. 146, p. 184-197European research projects
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