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首页> 外文期刊>The European Journal of Neuroscience >Age-related changes of anandamide metabolism in CB1 cannabinoid receptor knockout mice: correlation with behaviour.
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Age-related changes of anandamide metabolism in CB1 cannabinoid receptor knockout mice: correlation with behaviour.

机译：CB1大麻受体敲除小鼠中与年龄有关的Anandamide代谢变化：与行为的相关性。

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摘要

Anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) are the most active endocannabinoids at brain (CB1) cannabinoid receptors. CD1 mice lacking the CB1 receptors ("knockout" [KO] mutants) were compared with wildtype (WT) littermates for their ability to degrade AEA through an AEA membrane transporter (AMT) and an AEA hydrolase (fatty acid amide hydrolase, FAAH). The age dependence of AMT and FAAH activity were investigated in 1- or 4-month-old WT and KO animals, and found to increase with age in KO, but not WT, mice and to be higher in the hippocampus than in the cortex of all animals. AEA and 2-AG were detected in nmol/mg protein (microm) concentrations in both regions, though the hippocampus showed approximately twice the amount found in the cortex. In the same regions, 2-AG failed to change across groups, while AEA was significantly decreased (approximately 30%) in hippocampus, but not in cortex, of old KO mice, when compared with young KO or age-matched WT animals. In the open-field test under bright light and in the lit-dark exploration model of anxiety, young KO mice, compared with old KO, exhibited a mild anxiety-related behaviour. In contrast, neither the increase in memory performance assessed by the object recognition test, nor the reduction of morphine withdrawal symptoms, showed age dependence in CB1 KO mice. These results suggest that invalidation of the CB1 receptor gene is associated with age-dependent adaptive changes of endocannabinoid metabolism which appear to correlate with the waning of the anxiety-like behaviour exhibited by young CB1 KO mice.
机译：花生四烯酸（N-花生四烯酸乙醇胺，AEA）和2-花生四烯酸甘油酯（2-AG）是大脑中最活跃的内源性大麻素（CB1）大麻素受体。将缺乏CB1受体（“敲除” [KO]突变体）的CD1小鼠与野生型（WT）同窝仔小鼠通过AEA膜转运蛋白（AMT）和AEA水解酶（脂肪酸酰胺水解酶，FAAH）降解AEA的能力进行了比较。在1或4个月大的WT和KO动物中研究了AMT和FAAH活性的年龄依赖性，结果发现KO小鼠的年龄随AMT和FAAH活性的增加而增加，而WT小鼠则不随WT的增加而增加，海马的这一比例高于皮质所有的动物。在两个区域中均以nmol / mg蛋白（微米）浓度检测到了AEA和2-AG，尽管海马显示出的皮质中含量约为其两倍。在同一地区，与年轻的KO或年龄匹配的WT动物相比，成年KO小鼠的海马区AAG显着降低（约30％），而各组的2-AG均未改变，而AEA则显着降低（约30％）。在强光下的野外试验和焦虑的明暗探索模型中，与老KO相比，年轻的KO小鼠表现出轻度的焦虑相关行为。相反，通过对象识别测试评估的记忆性能的提高或吗啡戒断症状的减轻均未显示CB1 KO小鼠的年龄依赖性。这些结果表明，CB1受体基因的无效与内源性大麻素代谢的年龄依赖性适应性变化有关，后者似乎与年轻的CB1 KO小鼠表现出的焦虑样行为的减弱有关。

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