Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Stony Brook University Pain and Analgesia Research Center (SPARC), Department of Anesthesiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
Cells. 2022 Jun 16;11(12):1943. doi: 10.3390/cells11121943.
Even in the era of effective antiretroviral therapies, people living with Human Immunodeficiency Virus (HIV) are burdened with debilitating neurological dysfunction, such as HIV-associated neurocognitive disorders (HAND) and HIV-associated pain, for which there are no FDA approved treatments. Disruption to the neural circuits of cognition and pain in the form of synaptic degeneration is implicated in developing these dysfunctions. Glia-mediated synaptic pruning is a mechanism of structural plasticity in the healthy central nervous system (CNS), but recently, it has been discovered that dysregulated glia-mediated synaptic pruning is the cause of synaptic degeneration, leading to maladaptive plasticity and cognitive deficits in multiple diseases of the CNS. Considering the essential contribution of activated glial cells during the development of HAND and HIV-associated pain, it is possible that glia-mediated synaptic pruning is the causative mechanism of synaptic degeneration induced by HIV. This review will analyze the known examples of synaptic pruning during disease in order to better understand how this mechanism could contribute to the progression of HAND and HIV-associated pain.
即使在有效的抗逆转录病毒疗法时代，人类免疫缺陷病毒 (HIV) 感染者仍承受着衰弱的神经功能障碍的负担，如与 HIV 相关的认知障碍 (HAND) 和 HIV 相关的疼痛，而这些疾病目前尚无 FDA 批准的治疗方法。以突触退化的形式，认知和疼痛的神经回路的破坏与这些功能障碍的发展有关。神经胶质细胞介导的突触修剪是健康中枢神经系统 (CNS) 结构可塑性的一种机制，但最近发现，神经胶质细胞介导的突触修剪失调是突触退化的原因，导致 CNS 多种疾病的适应性不良性和认知缺陷。考虑到活化的神经胶质细胞在 HAND 和 HIV 相关疼痛的发展中的重要贡献，神经胶质细胞介导的突触修剪可能是 HIV 诱导的突触退化的致病机制。本综述将分析疾病过程中已知的突触修剪的例子，以更好地了解这种机制如何促进 HAND 和 HIV 相关疼痛的进展。
