Sex Differences in the Expression of Neuroimmune Molecules in the Spinal Cord of a Mouse Model of Antiretroviral-Induced Neuropathic Pain

Nucleoside reverse transcriptase inhibitors (NRTIs), drugs used to treat HIV infection, can cause neuropathic pain (NP) and neuroinflammation. An NRTI, 2′-3′-dideoxycytidine (ddC), was reported to induce mechanical allodynia and increase proinflammatory cytokines in the brains of female mice. In som...

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Main Authors: Maryam W. Al-HadlaQ, Willias Masocha
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/11/3/875
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author Maryam W. Al-HadlaQ
Willias Masocha
author_facet Maryam W. Al-HadlaQ
Willias Masocha
author_sort Maryam W. Al-HadlaQ
collection DOAJ
description Nucleoside reverse transcriptase inhibitors (NRTIs), drugs used to treat HIV infection, can cause neuropathic pain (NP) and neuroinflammation. An NRTI, 2′-3′-dideoxycytidine (ddC), was reported to induce mechanical allodynia and increase proinflammatory cytokines in the brains of female mice. In some models of NP, microglia activation is important for NP pathophysiology in male mice, while T cells are important in female mice. Age-matched female and male mice (BALB/c strain) treated intraperitoneally once daily with ddC for 5 days developed mechanical allodynia. Treatment with ddC increased <i>Cd11b</i>, <i>H2-Aa</i>, <i>Cd3e</i>, <i>Mapk1</i>, <i>Il1b</i>, <i>Tnf</i>, and <i>Il10</i> mRNA levels in the spinal cords of female, but not male, mice, whereas there was no alteration found in <i>Gfap</i> and <i>Mapk14</i> transcripts in both sexes on day 7 after ddC administration. The protein expression of CD11b and phospho-p38 MAPK was significantly increased in the spinal cords of ddC-treated female, but not male, mice, whereas Iba1 protein was elevated in ddC-treated male mice. There was no change in GFAP, CD3e, and phospho-p44/42 MAPK protein levels in both sexes. Thus, changes in neuroimmune cells and molecules in the spinal cords during ddC-induced neuroinflammation were sex-dependent, with female mice being more prone to neuroimmune changes than male mice.
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spelling doaj.art-8f0a0d95db754cf3b73be2c665e26a832023-11-17T09:46:54ZengMDPI AGBiomedicines2227-90592023-03-0111387510.3390/biomedicines11030875Sex Differences in the Expression of Neuroimmune Molecules in the Spinal Cord of a Mouse Model of Antiretroviral-Induced Neuropathic PainMaryam W. Al-HadlaQ0Willias Masocha1Molecular Biology Program, College of Graduate Studies, Kuwait University, Safat 13110, KuwaitDepartment of Pharmacology and Therapeutics, College of Pharmacy, Kuwait University, Safat 13110, KuwaitNucleoside reverse transcriptase inhibitors (NRTIs), drugs used to treat HIV infection, can cause neuropathic pain (NP) and neuroinflammation. An NRTI, 2′-3′-dideoxycytidine (ddC), was reported to induce mechanical allodynia and increase proinflammatory cytokines in the brains of female mice. In some models of NP, microglia activation is important for NP pathophysiology in male mice, while T cells are important in female mice. Age-matched female and male mice (BALB/c strain) treated intraperitoneally once daily with ddC for 5 days developed mechanical allodynia. Treatment with ddC increased <i>Cd11b</i>, <i>H2-Aa</i>, <i>Cd3e</i>, <i>Mapk1</i>, <i>Il1b</i>, <i>Tnf</i>, and <i>Il10</i> mRNA levels in the spinal cords of female, but not male, mice, whereas there was no alteration found in <i>Gfap</i> and <i>Mapk14</i> transcripts in both sexes on day 7 after ddC administration. The protein expression of CD11b and phospho-p38 MAPK was significantly increased in the spinal cords of ddC-treated female, but not male, mice, whereas Iba1 protein was elevated in ddC-treated male mice. There was no change in GFAP, CD3e, and phospho-p44/42 MAPK protein levels in both sexes. Thus, changes in neuroimmune cells and molecules in the spinal cords during ddC-induced neuroinflammation were sex-dependent, with female mice being more prone to neuroimmune changes than male mice.https://www.mdpi.com/2227-9059/11/3/875antiretroviral drugddCsex differencesneuroinflammationgene expressionprotein expression
spellingShingle Maryam W. Al-HadlaQ
Willias Masocha
Sex Differences in the Expression of Neuroimmune Molecules in the Spinal Cord of a Mouse Model of Antiretroviral-Induced Neuropathic Pain
Biomedicines
antiretroviral drug
ddC
sex differences
neuroinflammation
gene expression
protein expression
title Sex Differences in the Expression of Neuroimmune Molecules in the Spinal Cord of a Mouse Model of Antiretroviral-Induced Neuropathic Pain
title_full Sex Differences in the Expression of Neuroimmune Molecules in the Spinal Cord of a Mouse Model of Antiretroviral-Induced Neuropathic Pain
title_fullStr Sex Differences in the Expression of Neuroimmune Molecules in the Spinal Cord of a Mouse Model of Antiretroviral-Induced Neuropathic Pain
title_full_unstemmed Sex Differences in the Expression of Neuroimmune Molecules in the Spinal Cord of a Mouse Model of Antiretroviral-Induced Neuropathic Pain
title_short Sex Differences in the Expression of Neuroimmune Molecules in the Spinal Cord of a Mouse Model of Antiretroviral-Induced Neuropathic Pain
title_sort sex differences in the expression of neuroimmune molecules in the spinal cord of a mouse model of antiretroviral induced neuropathic pain
topic antiretroviral drug
ddC
sex differences
neuroinflammation
gene expression
protein expression
url https://www.mdpi.com/2227-9059/11/3/875
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