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

Adewale Adeluyi; Lindsey Guerin; Miranda L. Fisher; Ashley Galloway; Robert D. Cole; Sherine S.L. Chan; Michael D. Wyatt; Shannon W. Davis; Linnea R. Freeman; Pavel I. Ortinski; Jill R. Turner

doi:10.1126/sciadv.aax7031

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

Adewale Adeluyi
, Lindsey Guerin
, Miranda L. Fisher
, Ashley Galloway
, Robert D. Cole
, Sherine S.L. Chan
, Michael D. Wyatt
, Shannon W. Davis
, Linnea R. Freeman
, Pavel I. Ortinski
, Jill R. Turner

Research output: Contribution to journal › Article › peer-review

80 Scopus citations

Abstract

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.

Original language	English
Article number	aax7031
Journal	Science advances
Volume	5
Issue number	10
DOIs	https://doi.org/10.1126/sciadv.aax7031
State	Published - Oct 9 2019

Bibliographical note

Publisher Copyright:
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Funding

This work was supported by the National Institutes of Health–National Institute on Drug Abuse grants DA044311 and DA032681 to J.R.T., grants DA031747 and DA041513 to P.I.O., the NIDA T32 DA016176 (R.D.C.), and a Research Starter Grant from the PhRMA foundation to J.R.T.

Funders	Funder number
Pharmaceutical Research and Manufacturers of America Foundation
National Institutes of Health (NIH)
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse	R01DA044311, K99DA032681, K01DA031747, T32DA016176, R01DA041513

ASJC Scopus subject areas

General

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10.1126/sciadv.aax7031

Cite this

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title = "Microglia morphology and proinflammatory signaling in the nucleus accumbens during nicotine withdrawal",

abstract = "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.",

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AU - Adeluyi, Adewale

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AU - Galloway, Ashley

AU - Cole, Robert D.

AU - Chan, Sherine S.L.

AU - Wyatt, Michael D.

AU - Davis, Shannon W.

AU - Freeman, Linnea R.

AU - Ortinski, Pavel I.

AU - Turner, Jill R.

N1 - Publisher Copyright: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

PY - 2019/10/9

Y1 - 2019/10/9

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

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ASJC Scopus subject areas

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