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Behavioural brain research v.321, 2017년, pp.157 - 169   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Liraglutide prevents cognitive decline in a rat model of streptozotocin-induced diabetes independently from its peripheral metabolic effects

Palleria, Caterina (Science of Health Department, School of Medicine, University “Magna Graecia” of Catanzaro, Italy ) ; Leo, Antonio (Science of Health Department, School of Medicine, University “Magna Graecia” of Catanzaro, Italy ) ; Andreozzi, Francesco (Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100, Viale Europa, Catanzaro, Italy ) ; Citraro, Rita (Science of Health Department, School of Medicine, University “Magna Graecia” of Catanzaro, Italy ) ; Iannone, Michelangelo (CNR, Institute of Neurological Sciences, Pharmacology Section, Roccelletta di Borgia, Catanzaro, Italy ) ; Spiga, Rosangela (Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100, Viale Europa, Catanzaro, Italy ) ; Sesti, Giorgio (Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100, Viale Europa, Catanzaro, Italy ) ; Constanti, Andrew (Department of Pharmacology, UCL School of Pharmacy, 29/39 Brunswick Square, London, UK ) ; De Sarro, Giovambattista (Science of Health Department, School of Medicine, University “Magna Graecia” of Catanzaro, Italy ) ; Arturi, Franco (Department of Medical ) ; Russo, Emilio ;
  • 초록  

    Abstract Diabetes has been identified as a risk factor for cognitive dysfunctions. Glucagone like peptide 1 (GLP-1) receptor agonists have neuroprotective effects in preclinical animal models. We evaluated the effects of GLP-1 receptor agonist, liraglutide (LIR), on cognitive decline associated with diabetes. Furthermore, we studied LIR effects against hippocampal neurodegeneration induced by streptozotocin (STZ), a well-validated animal model of diabetes and neurodegeneration associated with cognitive decline. Diabetes and/or cognitive decline were induced in Wistar rats by intraperitoneal or intracerebroventricular injection of STZ and then rats were treated with LIR (300μg/kg daily subcutaneously) for 6 weeks. Rats underwent behavioral tests: Morris water maze, passive avoidance, forced swimming (FST), open field, elevated plus maze, rotarod tests. Furthermore, LIR effects on hippocampal neurodegeneration and mTOR pathway (AKT, AMPK, ERK and p70S6K) were assessed. LIR improved learning and memory only in STZ-treated animals. Anxiolytic effects were observed in all LIR-treated groups but pro- depressant effects in CTRL rats were observed. At a cellular/molecular level, intracerebroventricular STZ induced hippocampal neurodegeneration accompanied by decreased phosphorylation of AMPK, AKT, ERK and p70S6K. LIR reduced hippocampal neuronal death and prevented the decreased phosphorylation of AKT and p70S6K; AMPK was hyper- phosphorylated in comparison to CTRL group, while LIR had no effects on ERK. LIR reduced animal endurance in the rotarod test and this effect might be also linked to a reduction in locomotor activity during only the last two minutes of the FST. LIR had protective effects on cognitive functions in addition to its effects on blood glucose levels. LIR effects in the brain also comprised anxiolytic and pro -depressant actions (although influenced by reduced endurance). Finally, LIR protected from diabetes-dependent hippocampal neurodegeneration likely through an effect on mTOR pathway. Highlights Liraglutide might have anxiolytic and pro-depressant effects. Liraglutide demonstrated neuroprotective effects and improved learning and memory. Liraglutide protected from hippocampal neurodegeneration likely through mTOR pathway. Liraglutide reduced hippocampal neuronal death. Liraglutide treatment might be a relevant option for cognitive decline. Graphical abstract [DISPLAY OMISSION]


  • 주제어

    Streptozotocin .   Diabetes mellitus .   Rats .   Cognitive functions .   Neurodegeneration .   GLP-1 receptors .   Liraglutide .   mTOR signaling.  

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