Inflammatory Macrophages Promotes Development of Diabetic Encephalopathy

Abstract

Background/Aims: Diabetes and Alzheimer's disease are often associated with each other, whereas the relationship between two diseases is ill-defined. Although hyperglycemia during diabetes is a major cause of encephalopathy, diabetes may also cause chronic inflammatory complications including peripheral neuropathy. Hence the role and the characteristics of inflammatory macrophages in the development of diabetic encephalopathy need to be clarified. Methods: Diabetes were induced in mice by i.p. injection of streptozotocin (STZ). Two weeks after STZ injection and confirmation of development of diabetes, inflammatory macrophages were eliminated by i.p. injection of 20µg saporin-conjugated antibody against a macrophage surface marker CD11b (saporin-CD11b) twice per week, while a STZ-treated group received injection of rat IgG of same frequency as a control. The effects of macrophage depletion on brain degradation markers, brain malondialdehyde (MDA), catalase, superoxidase anion-positive cells and nitric oxide (NO) were measured. Results: Saporin-CD11b significantly reduced inflammatory macrophages in brain, without affecting mouse blood glucose, serum insulin, glucose responses and beta cell mass. However, reduced brain macrophages significantly inhibited the STZ-induced decreases in brain MDA, catalase and superoxidase anion-positive cells, and the STZ-induced decreases in brain NO. Conclusion: Inflammatory macrophages may promote development of diabetic encephalopathy.

TIPE2 Alleviates Systemic Lupus Erythematosus Through Regulating Macrophage Polarization

“…The M1 macrophages express nitric oxide synthase (iNOS) and some pro-inflammatory cytokines and toxin like reactive oxygen species (ROS) [34][35][36][37]. M2 macrophages are specified as expression of arginase, and surface markers CD163, CD206 and CD301 that are not expressed by M1 macrophages [11,23,24,26,[34][35][36][37][38][39][40]. Macrophage polarization has been shown to regulate a variety of biological processes, as recently nicely reviewed [41][42][43].…”

Autophagy of macrophages is regulated by PI3k/Akt/mTOR signalling in the development of diabetic encephalopathy

“…Although chronic hyperglycemia is the main trigger for the development of DE, past studies have shown that inflammatory damage to the brain also predisposes to disease progression [ 8 ]. Recently, in a mouse STZ-induced diabetes model, we have shown the centrality of recruited and infiltrated inflammatory macrophages in the mouse brain, to the progression of DE [ 9 ]. In the current study, our first aim was to investigate if this recruitment and infiltration of inflammatory macrophages in the brain are similarly required for DE development in diabetic rats, an animal model that more closely resembles human diabetes [ 26 ].…”

“…Past studies have shown that diabetic encephalopathy (DE) is caused primarily by constitutive hyperglycemia [ 2 ], although recent evidence suggests that oxidative stress and brain inflammation promote the development of DE and associated neurodegenerative diseases [ 3 – 7 ], highlighting a specific role for activated infiltrating macrophages in disease progression [ 8 ]. Recently, we reported that DE could be suppressed through depletion of inflammatory macrophages, without affecting the underlying diabetic status [ 9 ]. However, the molecular regulation of inflammatory macrophages in diabetes is unknown.…”

The Impact of Microbiota-Gut-Brain Axis on Diabetic Cognition Impairment

“…With study progressing, this nature has been recognized to play an important role in the development of DCI. There is a study demonstrated that macrophage activation and infiltration in the nervous system can lead to chronic degenerative disease of the central nervous system (Kierdorf et al, 2010), and blockade the activation of macrophage can significantly decrease levels of malondialdehyde, catalase and superoxide-positive cells in the brain (Wang et al, 2015). …”