Δ(9)-Tetrahydrocannabinol changes the brain lipidome and transcriptome differentially in the adolescent and the adult.
Δ(9)-Tetrahydrocannabinol changes the brain lipidome and transcriptome differentially in the adolescent and the adult.
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DOI：
10.1016/j.bbalip.2018.02.001
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Bradshaw HB
中科院分区：
文献类型：
--
作者：
Leishman E;Murphy M;Mackie K;Bradshaw HB
将青少年的大脑暴露于药物滥用中与成人发病精神病理的风险增加有关。大麻的使用在青春期达到高峰，对发育中的大脑有很大程度上未知的影响。大麻的主要精神活性成分Δ9-tetrahydrocannabinol （THC）改变神经元、星形胶质细胞和小胶质细胞信号。因此，单剂量四氢大麻酚会影响多种细胞和信号通路。内源性大麻素（eCBs）、n -花生四烯醇乙醇胺（AEA）和2-花生四烯醇甘油（2-AG）是一个相互连接的脂质组的成员，其中包括一类新兴的AEA结构类似物、脂胺、附加的2-酰基甘油、游离脂肪酸和前列腺素（pg）。脂质组中的脂质共享许多生物合成和代谢途径，但具有不同的信号传导特性。在这里，我们发现急性四氢大麻酚驱动了雌性小鼠大脑8个区域脂质组的年龄依赖性变化。有趣的是，大多数变化在成人中观察到，eCBs和相关脂质主要下降。对四氢大麻酚及其代谢物的分析显示，这些脑区分布不均；然而，在所有年龄组中，海马体（HIPP）中测量的THC水平最高。急性四氢大麻酚后的HIPP转录组学分析显示，与脂质组一样，成人转录组的变化明显大于青少年。重要的是，31个基因的调控在青少年和成人之间重叠，表明HIPP对四氢大麻酚暴露的转录组反应与年龄无关。综上所述，这些数据表明，首次接触单剂量的四氢大麻酚对中枢神经系统的信号传导有深远的影响。
Exposing the adolescent brain to drugs of abuse is associated with increased risk for adult onset psychopathologies. Cannabis use peaks during adolescence, with largely unknown effects on the developing brain. Cannabis’ major psychoactive component, Δ9-tetrahydrocannabinol (THC) alters neuronal, astrocytic, and microglial signaling. Therefore, multiple cellular and signaling pathways are affected with a single dose of THC. The endogenous cannabinoids (eCBs), N-arachidonoyl ethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG) are members of an interconnected lipidome that includes an emerging class of AEA structural analogs, the lipoamines, additional 2-acyl glycerols, free fatty acids, and prostaglandins (PGs). Lipids in this lipidome share many biosynthetic and metabolic pathways, yet have diverse signaling properties. Here, we show that acute THC drives age-dependent changes in this lipidome across 8 regions of the female mouse brain. Interestingly, most changes are observed in the adult, with eCBs and related lipids predominately decreasing. Analysis of THC and metabolites reveals an unequal distribution across these brain areas; however, the highest levels of THC were measured in the hippocampus (HIPP) in all age groups. Transcriptomic analysis of the HIPP after acute THC showed that like the lipidome, the adult transcriptome demonstrated significantly more changes than the adolescent. Importantly, the regulation of 31 genes overlapped between the adolescent and the adult, suggesting a conserved transcriptomic response in the HIPP to THC exposure independent of age. Taken together these data illustrate that the first exposure to a single dose of THC has profound effects on signaling in the CNS.
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影响因子：
7.3
作者：
De Petrocellis, Luciano;Ligresti, Alessia;Di Marzo, Vincenzo
通讯作者：
Di Marzo, Vincenzo
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
n-芳基多烯酰基甘氨酸，GPR55的另一种内源性激动剂。
DOI：
10.1016/j.bbrc.2017.07.038
发表时间：
2017-09-02
影响因子：
3.1
作者：
Console-Bram L;Ciuciu SM;Zhao P;Zipkin RE;Brailoiu E;Abood ME
通讯作者：
Abood ME
影响因子：
3.6
作者：
Cazade, Magali;Nuss, Cindy E.;Chemin, Jean
通讯作者：
Chemin, Jean
影响因子：
7.3
作者：
Burston, James J.;Wiley, Jenny L.;Sim-Selley, Laura J.
通讯作者：
Sim-Selley, Laura J.