Microglia morphology and proinflammatory signaling in the nucleus accumbens during nicotine withdrawal

被引：76

作者：

Adeluyi, Adewale ^{[1
]}

Guerin, Lindsey ^{[1
]}

Fisher, Miranda L. ^{[1
,2
]}

Galloway, Ashley ^{[3
]}

Cole, Robert D. ^{[3
,4
]}

Chan, Sherine S. L. ^{[5
,6
]}

Wyatt, Michael D. ^{[1
]}

Davis, Shannon W. ^{[7
]}

Freeman, Linnea R. ^{[8
]}

Ortinski, Pavel I. ^{[3
,4
]}

Turner, Jill R. ^{[1
,2
]}

机构：

[1] Univ South Carolina, Dept Drug Discovery & Biomed Sci, Columbia, SC 29208 USA

[2] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY USA

[3] Univ South Carolina, Sch Med, Dept Pharmacol Physiol & Neurosci, Columbia, SC 29208 USA

[4] Univ Kentucky, Sch Med, Dept Neurosci, Lexington, KY 40536 USA

[5] Med Univ South Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA

[6] Neuroene Therapeut, Mt Pleasant, SC USA

[7] Furman Univ, Dept Biol, Greenville, SC 29613 USA

[8] Univ South Carolina, Dept Biol Sci, Columbia, SC 29208 USA

来源：

SCIENCE ADVANCES | 2019年 / 5卷 / 10期

基金：

美国国家卫生研究院;

关键词：

RECEPTOR PARTIAL AGONIST; ANXIETY-LIKE BEHAVIOR; OXIDATIVE STRESS; PARKINSONS-DISEASE; SMOKING-CESSATION; NADPH OXIDASE; ACTIVATION; MECAMYLAMINE; VARENICLINE; MEMORY;

D O I：

10.1126/sciadv.aax7031

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Smoking is the largest preventable cause of death and disease in the United States. However, <5% of quit attempts are successful, underscoring the urgent need for novel therapeutics. Microglia are one untapped therapeutic target. While previous studies have shown that microglia mediate both inflammatory responses in the brain and brain plasticity, little is known regarding their role in nicotine dependence and withdrawal phenotypes. Here, we examined microglial changes in the striatum-a mesolimbic region implicated in the rewarding effects of drugs and the affective disruptions occurring during withdrawal. We show that both nicotine and withdrawal induce microglial morphological changes; however, proinflammatory effects and anxiogenic behaviors were observed only during nicotine withdrawal. Pharmacological microglial depletion during withdrawal prevented these effects. These results define differential effects of nicotine and withdrawal on inflammatory signaling in the brain, laying the groundwork for development of future smoking cessation therapeutics.

引用

页数：11

共 67 条

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