Abstract
The development of diabetic encephalopathy (DE) is enhanced by inflammatory macrophages, and is suppressed by macrophage autophagy. However, the molecular signaling that controls macrophage autophagy in DE remains ill-defined. Here, DE is induced in rats that received intraperitoneal injection of streptozotocin (STZ). In macrophages isolated from the brain of the rats, we detected downregulated autophagy activity and enhanced PI3k/Akt/mTOR/S6K1 signaling. In order to examine the role of autophagy and PI3k/Akt/mTOR signaling in DE development, an mTOR inhibitor, rapamycin, or an autophagy inhibitor, chloroquine (CQ), were administered to the rats that that received STZ. We found that rapamycin significantly enhanced DE development through mTOR suppression-induced augmentation of macrophage autophagy, while CQ significantly decreased DE development through suppression of macrophage autophagy. Together, our data suggest that PI3k/Akt/mTOR signaling may promote the development of DE through suppression of macrophage autophagy.
Highlights
Impairment of central nervous system function often occurs as a severe complication of diabetes [1]
Since brain macrophage autophagy is decreased in STZtreated rats, we investigated the activities of PI3k, AKT, mTOR and S6K1 in brain macrophages
Chronic hyperglycemia is the main trigger for the development of diabetic encephalopathy (DE), past studies have shown that inflammatory damage to the brain predisposes to disease progression [8]
Summary
Impairment of central nervous system function often occurs as a severe complication of diabetes [1]. Autophagy comprises the phagocytic degradation of lysosomes, as a recycling system within the cell, and as an important defense mechanism of the body [10]. Autophagy status influences the cell’s specific function. Macrophages bind to www.aging-us.com www.aging-us.com lysosomes through autophagy, eliminating, degrading and digesting damaged, degenerated, senescent and dysfunctional cellular components: cells and organelles, denatured proteins, nucleic acids and other biological macromolecules [16]. This function provides essential raw material for cellular reconstruction, regeneration and repair, enabling the recycling of intracellular resources [16]. Chloroquine (CQ) prevents autophagosomal degradation in late phase autophagy [22]
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