HIV and cocaine use leads to loss of astrocyte neurotrophic support and impaired lipid homeostasis in the brain

总结 星形胶质细胞和神经元之间的紧密代谢耦合涉及星形胶质细胞感知神经元应力 并通过摄取含有过量过氧化脂肪酸（FA）的脂质样颗粒来响应 在压力下。在应激条件下，活性氧（ROS）的产生诱导了细胞凋亡。 FA在神经元中的过氧化作用。神经元对有毒的过氧化FA高度敏感， 星形胶质细胞、神经元形成脂滴（LD）以包裹有毒FA的能力低。此外，委员会认为， 神经元线粒体不能有效地消耗作为能量来源的FA。因此，神经元排出 携带脂肪酸的类脂质颗粒星形胶质细胞用FA内吞脂质样颗粒，将其递送到 ER用于包装成脂滴（LD）以保护细胞免受有毒FA的侵害。LD还提供导管 用于将FA递送至星形胶质细胞线粒体，以在应激期间用作替代能量来源。在 在正常情况下，星形胶质细胞使用葡萄糖而不是FA作为其储备能量的主要来源。 正常情况下。星形胶质细胞和神经元之间的代谢协调对于CNS至关重要 功能和脂质稳态。然而，脂代谢的星形胶质细胞-神经元偶联的变化， 艾滋病毒和可卡因的使用是未知的。众所周知，有毒的过氧化脂肪酸（FA） 由应激神经元产生和排出的脂滴被转移到星形胶质细胞脂滴（LD）， 脂蛋白颗粒。星形胶质细胞通过线粒体β-氧化消耗储存在LD中的FA。因此，在本发明中， 通过星形胶质细胞的神经元衍生的FA代谢的代谢保护神经元免受FA毒性。 破坏这种紧密协调的偶联代谢脂肪酸可能有助于增加 在HIV和HIV-AIDS之间的有害协同作用期间报告的星形胶质细胞能量代谢和神经元缺陷 感染和可卡因使用。

Summary Tight metabolic coupling between astrocytes and neurons involves astrocytes sensing neuronal stress and responding by taking up lipid-like particles containing excess peroxidated fatty acids (FA) generated during stress. During stressful conditions, the generation of reactive oxygen species (ROS) induce the peroxidation of FA in neurons. Neurons are highly sensitive to toxic peroxidated FA and unlike astrocytes, neurons have a low capacity to form lipid droplets (LD) to encase the toxic FA. Moreover, neuronal mitochondria are unable to efficiently consume FAs as an energy source. Thus, neurons expel lipid-like particles carrying the FAs. Astrocytes endocytose lipid-like particles with FA, deliver them to the ER for packaging into lipid droplets (LD) to protect the cell from the toxic FAs. LD also provide a conduit for delivery of FA to astrocyte mitochondria for use as an alternative energy source during stress. In normal conditions, astrocytes use glucose rather than FA as their main source of reserve energy under normal conditions. Metabolic coordination between astrocytes and neurons is critical for CNS functioning and lipid homeostasis. However, changes in astrocyte-neuron coupling for lipid metabolism in response to HIV and cocaine use is unknown. It is known that toxic, peroxidated fatty acids (FAs) produced and expelled by stressed neurons are transferred to astrocytic lipid droplets (LD) by lipoprotein particles. Astrocytes consume the FAs stored in LD via mitochondrial β-oxidation. Thus, metabolism of neuron-derived FA metabolism by astrocytes protects neurons from FA toxicity. Disruption of this tightly coordinated coupling to metabolize FAs likely contributes to the increased astrocytic energy metabolism and neuronal deficit reported during detrimental synergy between HIV infection and cocaine use.