GET73 Prevents Ethanol-Induced Neurotoxicity in Primary Cultures of Rat Hippocampal Neurons.

Aims: N-[(4-trifluoromethyl) benzyl] 4-methoxybutyramide (GET73) may be considered a promising therapeutic agent for the treatment of alcohol use disorders. The compound displayed anti-alcohol and anxiolytic properties in rat. In the present study, an in vitro experimental model of chronic ethanol t...

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Publicado en:Alcohol & Alcoholism. Supplement Vol. 51; no. 2; pp. 128 - 136
Autores principales: Tomasini, Maria C., Borelli, Andrea C., Beggiato, Sarah, Tanganelli, Sergio, Loche, Antonella, Cacciaglia, Roberto, Ferraro, Luca, Antonelli, Tiziana
Formato: pictorial research tables/charts Journal Article
Publicado: Oxford University Press / USA Mar2016
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Mar2016
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      pub: Oxford University Press / USA
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        10.1093/alcalc/agv094
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        atl: GET73 Prevents Ethanol-Induced Neurotoxicity in Primary Cultures of Rat Hippocampal Neurons.
      aug:
        au:
          Tomasini, Maria C.
          Borelli, Andrea C.
          Beggiato, Sarah
          Tanganelli, Sergio
          Loche, Antonella
          Cacciaglia, Roberto
          Ferraro, Luca
          Antonelli, Tiziana
        affil: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy
      sug:
        subj:
          Chromatography, High Pressure Liquid
          Ethanol Pharmacodynamics
          Ethanol Administration and Dosage
          Reactive Oxygen Species
          Ethanol
          Neurons
          Rats
          Culture
          Post Hoc Analysis
          Study Design
          Data Analysis
          Analysis of Variance
          Experimental Studies
      ab: Aims: N-[(4-trifluoromethyl) benzyl] 4-methoxybutyramide (GET73) may be considered a promising therapeutic agent for the treatment of alcohol use disorders. The compound displayed anti-alcohol and anxiolytic properties in rat. In the present study, an in vitro experimental model of chronic ethanol treatment was used to investigate the ability of the compound to counteract the ethanol-induced neurotoxicity. Methods: Primary cultures of rat hippocampal neurons were exposed to ethanol (75 mM; 4 days) and the neuroprotective effects of GET73 were assessed by evaluating cell viability, cell morphology, glutamate levels and reactive oxygen species production. Results: The exposure to ethanol induced a reduction of cell viability, an alteration of cytoskeleton, a decrease in extracellular glutamate levels and an increase of reactive oxygen species production. The addiction of GET73 (1 and 10 µM) 1 h before and during chronic ethanol exposure prevented all the above ethanol-induced effects. Based on the proposed GET73 mechanism of action, the effects of mGlu5 receptor negative allosteric modulator, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), on ethanol- induced reduction of cell viability were also assessed. The results indicated that the addiction of MPEP (100 µM) 1 h before and during chronic ethanol exposure prevented the ethanol-induced cell viability reduction. Conclusion: The present findings provide the first evidence that GET73 shows a neuroprotective role against ethanol-induced neurotoxicity in primary cultures of rat hippocampal neurons. Together with previous findings, these results suggest that GET73 possesses multifaceted properties thus lending further support to the significance of developing GET73 as a therapeutic tool for use in the treatment of alcohol use disorders.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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