Abstract
The brain is the most vulnerable organ to glucose fluctuations, as well as inflammation. Considering that cognitive impairment might occur at the early stage of diabetes, it is very important to identify key markers of early neuronal dysfunction. Our overall goal was to identify neuroinflammatory and molecular indicators of early cognitive impairment in diabetic mice. To confirm cognitive impairment in diabetic mice, series of behavioral tests were conducted. The markers related to cognitive decline were classified into the following two groups: Neuroinflammatory markers: IL-1β, IL-6, tumor necrosis factor-α (TNF-α) and genetic markers (Bdnf, Arc, Egr1) which were estimated in brain regions. Our studies showed a strong association between hyperglycemia, hyperinsulinemia, neuroinflammation, and cognitive dysfunction in T2DM mice model. Cognitive impairment recorded in diabetes mice were associated not only with increased levels of cytokines but also decreased Arc and Egr1 mRNA expression level in brain regions associated with learning process and memory formation. The results of our research show that these indicators may be useful to test new forms of treatment of early cognitive dysfunction associated not only with diabetes but other diseases manifesting this type of disorders. The significant changes in Arc and Egr1 gene expression in early stage diabetes create opportunities it possible to use them to track the progression of CNS dysfunction and also to differential disease diagnosis running with cognitive impairment.
Highlights
Published: 9 April 2021Diabetes (DM, diabetes mellitus) is a complex metabolic disorder which is characterized by hyperglycemia due to insulin insufficiency and/or insulin dysfunction
Significant changes in Arc and early growth response gene 1 (Egr1) memory gene expression in early stage diabetes create opportunities it possible to use them to track the progression of central nervous system (CNS) dysfunction and to differential disease diagnosis running with cognitive impairment
The mance, in verbal and complex information epidemiological studies show that those withmemory diabetes have poorer cognitiveprocessing performance, The results of our studies showed a positive correlation between indicators of diaparticularly in verbal memory and complex information processing [10]
Summary
Diabetes (DM, diabetes mellitus) is a complex metabolic disorder which is characterized by hyperglycemia due to insulin insufficiency and/or insulin dysfunction. Diabetes Federation and World Health Organization the observes increasing number of diabetes in the world and estimates that this trend will continue in the future [1]. Diabetes is a chronic disease which may lead to the development of numerous complications [2,3,4,5,6,7,8,9]. One of the most dangerous consequences of chronic hyperglycemia are problems in function of central nervous system (CNS) which are referred as “diabetic encephalopathy” and is characterized by cognitive impairment and motor dysfunctions [10]
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