Department of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
Department of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
Neurosci Lett. 2022 Jun 21;782:136688. doi: 10.1016/j.neulet.2022.136688. Epub 2022 May 17.
Nearly one-third of persons infected with HIV-1 (PWH) develop HIV-associated neurocognitive disorders (HAND), which can be exacerbated by exposure to opioids. The impact of opioids on HIV-induced alterations in neuronal plasticity is less well understood. Both morphine exposure and HIV have been shown to disrupt synaptic growth and stability in the hippocampus suggesting a potential site of convergence for their deleterious effects. In the present study, we examined the density of dendritic spines in CA1 and CA3 pyramidal neurons, and granule neurons within the dentate gyrus representing the hippocampal trisynaptic pathway after short-term exposure to the HIV transactivator of transcription (Tat) protein and morphine. We exposed inducible male, HIV-1 Tat transgenic mice to escalating doses of morphine (10-40 mg/kg, b.i.d.) and examined synaptodendritic structure in Golgi-impregnated hippocampal neurons. HIV-1 Tat, but not morphine, systematically reduced the density of apical, but not basilar, dendrites of CA1 and CA3 pyramidal neurons, and granule neuronal apical dendrites, suggesting the coordinated loss of specific synaptic interconnections throughout the hippocampal trisynaptic pathway.
将近三分之一的人类免疫缺陷病毒 1 型（HIV-1）感染者（PWH）会发展为与 HIV 相关的神经认知障碍（HAND），而接触阿片类药物会使这种情况恶化。阿片类药物对 HIV 引起的神经元可塑性改变的影响还不太清楚。吗啡暴露和 HIV 都已被证明会破坏海马体中的突触生长和稳定性，这表明它们的有害影响可能存在一个共同作用的部位。在本研究中，我们研究了 CA1 和 CA3 锥体神经元以及齿状回内颗粒神经元中的树突棘密度，这些神经元代表了海马体三突触通路，研究对象为短期暴露于 HIV 转录激活蛋白（Tat）蛋白和吗啡后的雄性诱导型 HIV-1 Tat 转基因小鼠。我们使 HIV-1 Tat 转基因雄性小鼠接触递增剂量的吗啡（10-40mg/kg，每天两次），并检查了高尔基浸渍海马神经元中的突触树突结构。HIV-1 Tat 而非吗啡会系统性地降低 CA1 和 CA3 锥体神经元以及颗粒神经元的树突棘密度，但其只降低了树突的顶段而非基段，这表明在整个海马体三突触通路中，特定的突触连接协同丧失。
