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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MDPI AG
2023-03-01
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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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