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Protective Effects of N-Oleoylglycine in a Mouse Model of Mild Traumatic Brain Injury.
ACS Chemical Neuroscience ( IF 5 ) Pub Date : 2020-02-04 , DOI: 10.1021/acschemneuro.9b00633
Fabiana Piscitelli 1 , Francesca Guida 2 , Livio Luongo 2 , Fabio Arturo Iannotti 1 , Serena Boccella 2 , Roberta Verde 1 , Anna Lauritano 1 , Roberta Imperatore 3 , Reem Smoum 4 , Luigia Cristino 1 , Aron H Lichtman 5 , Linda A Parker 6 , Raphael Mechoulam 4 , Sabatino Maione 2 , Vincenzo Di Marzo 1, 7
Affiliation  

Traumatic brain injury (TBI) is one of the main cause of death in young people and currently no drugs to treat brain injury exist. Recently, we have reported that mice with mild-TBI with a specific injury in the insula, showed elevated levels of a little investigated N-acyl amino acid, the N-oleoyl-glycine (OlGly). N-acyl-amino acids have recently gained increased interest because of their important biological activities, moreover, they belong to the lipoaminoacids family and have structural similarities with the endocannabinoids (eCBs). The aim of this study was to test the neuroprotective and anti-hyperalgesic actions of OlGly in a model of mouse mild-TBI (mTBI) and its effect on levels of eCBs and N-acylethanolamines at the end of treatment. Following mTBI, the mice were administered a daily injection of OlGly (10-50-100 mg/kg i.p.) for 14 days. Treatment with OlGly normalized motor impairment and behavior in the light/dark box test; ameliorated TBI-induced thermal hyperalgesia and mechanical allodynia and normalized aggressiveness and depression. Moreover, levels of eCBs and some N-acylethanolamines underwent significant changes 60 days after TBI, especially in the prefrontal cortex and in the hypothalamus, and OlGly reversed some of these changes. In conclusion, our findings reveal that OlGly ameliorates the behavioral alterations associated with mTBI, whilst concomitantly modulating eCB and eCB-like mediator tone.

中文翻译:

N-油酰甘氨酸在轻度创伤性脑损伤小鼠模型中的保护作用。

外伤性脑损伤(TBI)是年轻人死亡的主要原因之一,目前尚无治疗脑损伤的药物。最近,我们报道了患有轻度TBI且在岛内有特定损伤的小鼠,其经研究的N-酰基氨基酸N-油酰基-甘氨酸(OlGly)的水平升高。N-酰基氨基酸由于其重要的生物活性而最近引起人们的兴趣,此外,它们属于脂氨基酸家族,并且与内源性大麻素(eCBs)具有结构相似性。这项研究的目的是测试在小鼠轻度TBI(mTBI)模型中OlGly的神经保护和抗痛觉过敏作用及其对eCBs和N水平的影响-酰基乙醇胺在治疗结束时。在mTBI之后,每天给小鼠注射OlGly(10-50-100 mg / kg ip),持续14天。在明/暗盒测试中使用OlGly标准化的运动障碍和行为进行治疗; 改善了TBI引起的热痛觉过敏和机械性异常性疼痛,并使攻击和抑郁情绪正常化。此外,TBI后60天,eCB和某些N-酰基乙醇胺的水平发生了显着变化,尤其是在额叶前皮质和下丘脑中,OlGly逆转了其中一些变化。总之,我们的发现表明,OlGly改善了与mTBI相关的行为改变,同时调节了eCB和类似eCB的介体音调。
更新日期:2020-02-04
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