Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark.
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark.
Neurochem Int. 2019 May;125:7-15. doi: 10.1016/j.neuint.2019.01.023. Epub 2019 Feb 1.
Altered endocannabinoid (eCB) signalling is suggested as an important contributor to the pathophysiology of depression. To further elucidate this, we conducted a study using a genetic rat model of depression, the Flinders Sensitive Line (FSL), and their controls, the Flinders Resistant Line (FRL) rats. Plasma, right and left prefrontal cortex, and hippocampus were isolated from FSL and FRL rats. We analyzed each region for the eCB anandamide (AEA) and 2-arachidonoylglycerol (2-AG) levels by liquid chromatography/multiple reaction monitoring (LC/MRM), mRNA and protein levels of the cannabinoid type 1 receptor (CBR), fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) by real time qPCR and Western blotting. Content of 2-AG was lower in the left side of the hippocampus and prefrontal cortex in FSL rats compared to FRL rats. Inversely, levels of AEA were higher in right hippocampus than in left hippocampus. In plasma, AEA levels were increased and 2-AG decreased. Cannabinoid receptor 1 (Cnr1), Faah and Magl mRNA levels were prominently decreased in right prefrontal cortex of FSL rats as compared to FRL rats. Protein expression of CBR and FAAH were decreased in left hippocampus. In summary, our data suggest a decreased eCB signalling in the FSL rats, which could contribute to the depressive-like behaviour. Interestingly, the altered eCB system activity appear to be hemisphere-specific in the limbic regions. Our study support the existing literature and showed altered eCB system activity in this particular animal model of depression.
内源性大麻素（eCB）信号改变被认为是抑郁症病理生理学的重要贡献者。为了进一步阐明这一点，我们使用抑郁症的遗传大鼠模型，即弗林德斯敏感系（FSL）及其对照，弗林德斯抗性系（FRL）大鼠进行了一项研究。从 FSL 和 FRL 大鼠中分离出血浆、右侧和左侧前额皮质和海马体。我们通过液相色谱/多重反应监测（LC/MRM）分析每个区域的大麻素 1 型受体（CBR）、脂肪酸酰胺水解酶（FAAH）和单酰基甘油脂肪酶（MAGL）的 eCB 大麻素（AEA）和 2-花生四烯酸甘油（2-AG）水平，实时 qPCR 和 Western blotting 分析 mRNA 和蛋白水平。与 FRL 大鼠相比，FSL 大鼠左侧海马体和前额皮质的 2-AG 含量较低。相反，右侧海马体的 AEA 水平高于左侧海马体。在血浆中，AEA 水平升高，2-AG 水平降低。与 FRL 大鼠相比，FSL 大鼠右侧前额皮质的大麻素受体 1（Cnr1）、Faah 和 Magl mRNA 水平明显降低。左海马体的 CBR 和 FAAH 蛋白表达减少。总之，我们的数据表明 FSL 大鼠的 eCB 信号降低，这可能导致抑郁样行为。有趣的是，在边缘区域，改变的 eCB 系统活性似乎具有半球特异性。我们的研究支持现有文献，并表明在这种特定的抑郁症动物模型中改变了 eCB 系统的活性。
