Microglia Phenotypes Following the Induction of Alcohol Dependence in Adolescent Rats.
Microglia Phenotypes Following the Induction of Alcohol Dependence in Adolescent Rats.
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DOI：
10.1111/acer.14504
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Nixon K
中科院分区：
文献类型：
--
作者：
Peng H;Nixon K
先天性免疫系统的激活可能在酒精使用障碍(AUD)的发展中发挥作用，AUD通常源于青少年酗酒。小胶质细胞是先天免疫系统中的一个关键角色，它的激活发生在从促炎或M1样表型到抗炎或M2样表型的一系列表型上。青春期雄性大鼠每隔8h用乙醇或等热量对照饲料灌胃，连续4d，分别于0、2、7、14d处死动物。Percoll梯度离心法分离内嗅皮层和海马区小胶质细胞，表面抗原标记活化后进行流式细胞仪分析。小胶质细胞的极化状态定义为CD11b+CD45low细胞，由M1表面标志、主要组织相容性复合体(MHC)II、CD32和CD86以及M2表面标志CD206(甘露糖受体)的表达决定。逆转录聚合酶链式反应检测细胞因子基因表达。根据CD11b免疫反应，分离的细胞是高度浓缩的小胶质细胞/巨噬细胞群(纯度为95%)。小胶质细胞活化标志物CD11b和CD45、M1(MHC-II)和M2(CD206)在T2时表现为最显著的增加，而另外的M1标记CD86和CD32也增加了。令人惊讶的是，除IL-6和肿瘤坏死因子-α在两个时间点均无变化外，在乙醇大鼠的各个时间点，致炎基因CCL_2、IL-1？、IL-6和肿瘤坏死因子-α的表达普遍降低。同时，在T2和T7，BDNF的表达增加，而IGF1和转化生长因子β基因的表达降低。海马区精氨酸酶在T0时也有升高，但酒精对其无明显影响。总之，这些数据支持酒精依赖后的小胶质细胞表型不是简单的M1或M2表型，尽管观察到了更多的抗炎表型。确定小胶质细胞的表型对于了解它们在AUDS发生发展中的作用至关重要。
Activation of the innate immune system may play a role in the development of alcohol use disorders (AUDs), which often originate with adolescent alcohol abuse. A key player in the innate immune system is microglia, the activation of which occurs along a spectrum from pro-inflammatory, or M1-like, to anti-inflammatory, or M2-like, phenotypes. Adolescent, male rats were gavaged with ethanol or isocaloric control diet every 8 hours for 4 days, then sacrificed at 0, 2, 7, and 14 days later. Microglia were isolated from the entorhinal cortex and hippocampus by Percoll gradient centrifugation, labeled with surface antigens for activation and analyzed by flow cytometry. Polarization states of microglia, defined as CD11b+CD45low cells, were determined by the expression of M1 surface markers, major histocompatibility complex (MHC) II, CD32, and CD86, and M2 surface marker, CD206 (mannose receptor). Cytokine gene expression was measured by reverse transcriptase polymerase chain reaction. Isolated cells were a highly enriched population (>95% pure) of microglia/macrophages according to CD11b immunoreactivity. Ethanol rats showed the most dramatic increases in microglia activation markers CD11b and CD45, and M1 (MHC-II) and M2 (CD206) markers at T2, when additional M1 markers CD86 and CD32 were also increased. Surprisingly, pro-inflammatory gene expression of CCL2, IL-1ß, IL-6 and TNF-α, generally was decreased at all time points in ethanol rats except for IL-6 which was increased at T0 and TNF-α which was not changed at T0 in either region. Simultaneously, BDNF expression was increased at T2 and T7 while IGF1 and TGF-ß gene expression were decreased. Arginase was also increased at T0 in hippocampus, but not changed by alcohol otherwise. Altogether, these data support that microglia phenotype after alcohol dependence is not a simple M1 or M2 phenotype, though more indicators of an anti-inflammatory phenotype were observed. Determining microglia phenotype is critical for understanding their role in the development of AUDs.
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影响因子：
9.3
作者：
Cherry JD;Olschowka JA;O'Banion MK
通讯作者：
O'Banion MK
DOI：
10.1523/jneurosci.3295-09.2010
发表时间：
2010-01-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Clark AK;Staniland AA;Marchand F;Kaan TK;McMahon SB;Malcangio M
通讯作者：
Malcangio M
乙醇差异调节BV2小胶质细胞中的P2X4和P2X7受体活性和功能。
影响因子：
4.7
作者：
Asatryan L;Ostrovskaya O;Lieu D;Davies DL
通讯作者：
Davies DL
影响因子：
10.6
作者：
Crews, Fulton T.;Qin, Liya;Sheedy, Donna;Vetreno, Ryan P.;Zou, Jian
通讯作者：
Zou, Jian
影响因子：
5.3
作者：
Alfonso-Loeches, Silvia;Pascual-Lucas, Maya;Guerri, Consuelo
通讯作者：
Guerri, Consuelo