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<p>The prevalent use of combination antiretroviral therapy (cART) in the treatment and as a preventative prophylaxis in HIV-exposed individuals has raised concern for its neurotoxicity. The diabetogenic effect of cART and alcohol consumption also warrants that cART cerebellar neurotoxicity be evaluated for its impact in a diabetic state. Therefore, the cerebellar effects of the interaction of cART and alcohol in diabetic disease conditions were assessed using a diabetic male Sprague Dawley rat model. Forty-eight adult male Sprague Dawley rats were divided into eight groups of six rats; untreated group (NC), cART alone group (AV), alcohol alone (AL), diabetes (DB), cART and alcohol&#xa0;treated (AVAL), diabetic cART treated group (AVDB), diabetic alcohol treated group (ALDB), and diabetic alcohol and cART treated group (AVALDB), treated for 90&#xa0;days and then terminated, brains excised, and homogenized. Cerebellar samples were analysed for MDA Elisa, Caspase 3, Bcl<sub>2</sub> and Occludin qPCR while Giemsa stain histology and Caspase 3 and cyclophilin A immunohistochemistry were also carried out on sectioned cerebellar tissue. Our results reveal increased oxidative stress and Caspase 3 mRNA in all treated groups, with elevated immunohistochemical Caspase 3 expression in Bergmann and cerebellar nuclei glial cells, but depleted cyclophilin A expression in these cells with AV and AVAL treatments. The AL, DB, AVDB, and AVALDB groups showed depleted occludin mRNA and elevated cyclophilin A expression in glial cells, while apoptotic Caspase 3 expression is observed mostly in the cerebellar nuclei neurons and Purkinje neurons of the diabetic groups (DB, AVDB, ALDB and AVALDB). These results indicate the potential of cART and alcohol interaction to impair cerebellar nuclei and cortex glial cells but in combination with diabetes induces Purkinje and dentate nucleus apoptosis with depleted cyclophilin A expression. Therefore, these crucial cells for cerebellar homeostasis and coordination function should be monitored where these factors co-occur.</p>

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Interactive effects of combination antiretroviral therapy (cART) and alcohol on the cerebellum of diabetic male Sprague Dawley rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月15日

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  • Jaclyn E. Asouzu Johnson,
  • Ejikeme F. Mbajiorgu

摘要

The prevalent use of combination antiretroviral therapy (cART) in the treatment and as a preventative prophylaxis in HIV-exposed individuals has raised concern for its neurotoxicity. The diabetogenic effect of cART and alcohol consumption also warrants that cART cerebellar neurotoxicity be evaluated for its impact in a diabetic state. Therefore, the cerebellar effects of the interaction of cART and alcohol in diabetic disease conditions were assessed using a diabetic male Sprague Dawley rat model. Forty-eight adult male Sprague Dawley rats were divided into eight groups of six rats; untreated group (NC), cART alone group (AV), alcohol alone (AL), diabetes (DB), cART and alcohol treated (AVAL), diabetic cART treated group (AVDB), diabetic alcohol treated group (ALDB), and diabetic alcohol and cART treated group (AVALDB), treated for 90 days and then terminated, brains excised, and homogenized. Cerebellar samples were analysed for MDA Elisa, Caspase 3, Bcl2 and Occludin qPCR while Giemsa stain histology and Caspase 3 and cyclophilin A immunohistochemistry were also carried out on sectioned cerebellar tissue. Our results reveal increased oxidative stress and Caspase 3 mRNA in all treated groups, with elevated immunohistochemical Caspase 3 expression in Bergmann and cerebellar nuclei glial cells, but depleted cyclophilin A expression in these cells with AV and AVAL treatments. The AL, DB, AVDB, and AVALDB groups showed depleted occludin mRNA and elevated cyclophilin A expression in glial cells, while apoptotic Caspase 3 expression is observed mostly in the cerebellar nuclei neurons and Purkinje neurons of the diabetic groups (DB, AVDB, ALDB and AVALDB). These results indicate the potential of cART and alcohol interaction to impair cerebellar nuclei and cortex glial cells but in combination with diabetes induces Purkinje and dentate nucleus apoptosis with depleted cyclophilin A expression. Therefore, these crucial cells for cerebellar homeostasis and coordination function should be monitored where these factors co-occur.