Abstract
The glymphatic system has emerged as an important player in central nervous system (CNS) diseases, by regulating the vasculature impairment, effectively controlling the clearance of toxic peptides, modulating activity of astrocytes, and being involved in the circulation of neurotransmitters in the brain. Recently, several studies have indicated decreased activity of the glymphatic pathway under diabetes conditions such as in insulin resistance and hyperglycemia. Furthermore, diabetes leads to the disruption of the blood-brain barrier and decrease of apolipoprotein E (APOE) expression and the secretion of norepinephrine in the brain, involving the impairment of the glymphatic pathway and ultimately resulting in cognitive decline. Considering the increased prevalence of diabetes-induced dementia worldwide, the relationship between the glymphatic pathway and diabetes-induced dementia should be investigated and the mechanisms underlying their relationship should be discussed to promote the development of an effective therapeutic approach in the near future. Here, we have reviewed recent evidence for the relationship between glymphatic pathway dysfunction and diabetes. We highlight that the enhancement of the glymphatic system function during sleep may be beneficial to the attenuation of neuropathology in diabetes-induced dementia. Moreover, we suggest that improving glymphatic system activity may be a potential therapeutic strategy for the prevention of diabetes-induced dementia.
Highlights
The relationship between type 2 diabetes mellitus (T2DM) and dementia, called “type 3 diabetes”, has emerged as a critical health issue across the world as it is fast increasing in incidence [1]
Considering previous evidence, we suggest that melatonin administration should be considered as an approach to reduce neuropathology in diabetes-induced dementia
In diabetes-induced dementia, the glymphatic system dysfunction characterized by the failure of interstitial solute clearance leads to extracellular solute accumulation and cognitive decline
Summary
The relationship between type 2 diabetes mellitus (T2DM) and dementia, called “type 3 diabetes”, has emerged as a critical health issue across the world as it is fast increasing in incidence [1]. Many T2DM patients have cognitive impairments [4] and even patients in the prediabetic stage of insulin resistance exhibit a decrease in memory function and dysfunction of cognitive flexibility and cognitive control [5]. Taking into consideration the previous evidence for the relationship between diabetes conditions, including insulin resistance and hyperglycemia, and cognitive decline [5], the neurological changes in diabetes-induced dementia should be investigated to elucidate the underlying mechanisms and support the design of appropriate therapy and prevention in clinical practice. We have reviewed recent evidence for the relationship between glymphatic pathway dysfunction and diabetes-induced dementia. We have suggested a therapeutic approach for alleviating the neuropathological symptoms of diabetes-induced dementia through the improvement of glymphatic system function
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