RT Journal Article
T1 Oleoylethanolamide restores alcohol-induced inhibition of neuronal proliferation and microglial activity in striatum.
A1 Rivera, Patricia
A1 Silva-Peña, Daniel
A1 Blanco, Eduardo
A1 Vargas, Antonio
A1 Arrabal, Sergio
A1 Serrano, Antonia
A1 Pavón, Francisco Javier
A1 Bindila, Laura
A1 Lutz, Beat
A1 Rodríguez de Fonseca, Fernando
A1 Suárez, Juan
K1 Alcohol
K1 Locomotion
K1 Microglia
K1 Neurogenesis
K1 PPARα
K1 Striatum
AB 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 ± 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.
YR 2018
FD 2018-11-26
LK http://hdl.handle.net/10668/13259
UL http://hdl.handle.net/10668/13259
LA en
DS RISalud
RD Apr 6, 2025