Acetylsalicylic acid reduces cigarette smoke withdrawal-induced anxiety in rats via modulating the expression of NFĸB, GLT-1, and xCT

Background: Chronic exposure to cigarette smoke produces neuroinflammation and long-term changes in neurotransmitter systems, especially glutamatergic systems.Objective: We examined the effects of cigarette smoke on astroglial glutamate transporters as well as NF-κB expression in mesocorticolimbic b...

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Main Authors: Alaa M. Hammad, Lujain F. Alzaghari, Malek Alfaraj, Walid Al-Qerem, Wamidh H. Talib, Fawaz Alasmari, Haneen Amawi, F. Scott Hall
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.1047236/full
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author Alaa M. Hammad
Lujain F. Alzaghari
Malek Alfaraj
Walid Al-Qerem
Wamidh H. Talib
Fawaz Alasmari
Haneen Amawi
F. Scott Hall
author_facet Alaa M. Hammad
Lujain F. Alzaghari
Malek Alfaraj
Walid Al-Qerem
Wamidh H. Talib
Fawaz Alasmari
Haneen Amawi
F. Scott Hall
author_sort Alaa M. Hammad
collection DOAJ
description Background: Chronic exposure to cigarette smoke produces neuroinflammation and long-term changes in neurotransmitter systems, especially glutamatergic systems.Objective: We examined the effects of cigarette smoke on astroglial glutamate transporters as well as NF-κB expression in mesocorticolimbic brain regions, prefrontal cortex (PFC) and nucleus accumbens (NAc). The behavioral consequences of cigarette smoke exposure were assessed using open field (OF) and light/dark (LD) tests to assess withdrawal-induced anxiety-like behavior.Methods: Sprague-Dawley rats were randomly assigned to five experimental groups: a control group exposed only to standard room air, a cigarette smoke exposed group treated with saline vehicle, two cigarette smoke exposed groups treated with acetylsalicylic acid (ASA) (15 mg/kg and 30 mg/kg, respectively), and a group treated only with ASA (30 mg/kg). Cigarette smoke exposure was performed for 2 h/day, 5 days/week, for 31 days. Behavioral tests were conducted weekly, 24 h after cigarette smoke exposure, during acute withdrawal. At the end of week 4, rats were given either saline or ASA 45 min before cigarette exposure for 11 days.Results: Cigarette smoke increased withdrawal-induced anxiety, and 30 mg/kg ASA attenuated this effect. Cigarette smoke exposure increased the relative mRNA and protein expression of nuclear factor ĸB (NFĸB) in PFC and NAc, and ASA treatment reversed this effect. Also, cigarette smoke decreased the relative mRNA and protein expression of glutamate transporter1 (GLT-1) and the cystine-glutamate transporter (xCT) in the PFC and the NAc, while ASA treatment normalized their expression.Conclusion: Cigarette smoke caused neuroinflammation, alterations in glutamate transporter expression, and increased anxiety-like behavior, and these effects were attenuated by acetylsalicylic acid treatment.
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spelling doaj.art-e477f1bafd1a437796d1a9f3ee65baf32023-01-09T15:08:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-01-011310.3389/fphar.2022.10472361047236Acetylsalicylic acid reduces cigarette smoke withdrawal-induced anxiety in rats via modulating the expression of NFĸB, GLT-1, and xCTAlaa M. Hammad0Lujain F. Alzaghari1Malek Alfaraj2Walid Al-Qerem3Wamidh H. Talib4Fawaz Alasmari5Haneen Amawi6F. Scott Hall7Department of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman, JordanDepartment of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman, JordanDepartment of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman, JordanDepartment of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman, JordanDepartment of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, JordanDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid, JordanDepartment of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, United StatesBackground: Chronic exposure to cigarette smoke produces neuroinflammation and long-term changes in neurotransmitter systems, especially glutamatergic systems.Objective: We examined the effects of cigarette smoke on astroglial glutamate transporters as well as NF-κB expression in mesocorticolimbic brain regions, prefrontal cortex (PFC) and nucleus accumbens (NAc). The behavioral consequences of cigarette smoke exposure were assessed using open field (OF) and light/dark (LD) tests to assess withdrawal-induced anxiety-like behavior.Methods: Sprague-Dawley rats were randomly assigned to five experimental groups: a control group exposed only to standard room air, a cigarette smoke exposed group treated with saline vehicle, two cigarette smoke exposed groups treated with acetylsalicylic acid (ASA) (15 mg/kg and 30 mg/kg, respectively), and a group treated only with ASA (30 mg/kg). Cigarette smoke exposure was performed for 2 h/day, 5 days/week, for 31 days. Behavioral tests were conducted weekly, 24 h after cigarette smoke exposure, during acute withdrawal. At the end of week 4, rats were given either saline or ASA 45 min before cigarette exposure for 11 days.Results: Cigarette smoke increased withdrawal-induced anxiety, and 30 mg/kg ASA attenuated this effect. Cigarette smoke exposure increased the relative mRNA and protein expression of nuclear factor ĸB (NFĸB) in PFC and NAc, and ASA treatment reversed this effect. Also, cigarette smoke decreased the relative mRNA and protein expression of glutamate transporter1 (GLT-1) and the cystine-glutamate transporter (xCT) in the PFC and the NAc, while ASA treatment normalized their expression.Conclusion: Cigarette smoke caused neuroinflammation, alterations in glutamate transporter expression, and increased anxiety-like behavior, and these effects were attenuated by acetylsalicylic acid treatment.https://www.frontiersin.org/articles/10.3389/fphar.2022.1047236/fullGLT-1XCTNFkBanxiety-like behavioracetylsalicylic acid
spellingShingle Alaa M. Hammad
Lujain F. Alzaghari
Malek Alfaraj
Walid Al-Qerem
Wamidh H. Talib
Fawaz Alasmari
Haneen Amawi
F. Scott Hall
Acetylsalicylic acid reduces cigarette smoke withdrawal-induced anxiety in rats via modulating the expression of NFĸB, GLT-1, and xCT
Frontiers in Pharmacology
GLT-1
XCT
NFkB
anxiety-like behavior
acetylsalicylic acid
title Acetylsalicylic acid reduces cigarette smoke withdrawal-induced anxiety in rats via modulating the expression of NFĸB, GLT-1, and xCT
title_full Acetylsalicylic acid reduces cigarette smoke withdrawal-induced anxiety in rats via modulating the expression of NFĸB, GLT-1, and xCT
title_fullStr Acetylsalicylic acid reduces cigarette smoke withdrawal-induced anxiety in rats via modulating the expression of NFĸB, GLT-1, and xCT
title_full_unstemmed Acetylsalicylic acid reduces cigarette smoke withdrawal-induced anxiety in rats via modulating the expression of NFĸB, GLT-1, and xCT
title_short Acetylsalicylic acid reduces cigarette smoke withdrawal-induced anxiety in rats via modulating the expression of NFĸB, GLT-1, and xCT
title_sort acetylsalicylic acid reduces cigarette smoke withdrawal induced anxiety in rats via modulating the expression of nfqb glt 1 and xct
topic GLT-1
XCT
NFkB
anxiety-like behavior
acetylsalicylic acid
url https://www.frontiersin.org/articles/10.3389/fphar.2022.1047236/full
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