期刊
NEUROPHARMACOLOGY
卷 146, 期 -, 页码 184-197出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2018.11.037
关键词
Alcohol; PPAR alpha; Microglia; Neurogenesis; Locomotion; Striatum
资金
- RETICS Red de Trastornos Adictivos, Instituto de Salud Carlos III (ISCIII)
- Ministerio de Economia y Competitividad
- European Regional Development Funds-European Union (ERDF-EU) [RD16/0017/0001]
- ISCIII, MINECO
- ERDF-EU [PI16/01374, PI16/01698, PI16/01953, PI17/02026]
- Ministerio de Sanidad, Servicios Sociales e Igualdad and Plan Nacional sobre Drogas [PNSD2015/047, PND2017/043]
- Consejeria de Economia, Innovacion y Ciencia, Junta de Andalucia
- Consejerfa de Salud, Junta de Andalucia
- German Research Foundation DFG [FOR926, CP14/00212, CP14/00173]
- Miguel Servet Program of ISCIII
- National System of Health, ISCIII
- FIMABIS [CPII17/00024]
- ISCIII, ERDF-EU [CD16/00067]
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.
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