Diabetes Mellitus-Related Neurobehavioral Deficits in Mice Are Associated With Oligodendrocyte Precursor Cell Dysfunction

Recent clinical studies demonstrated an increase of the incidence of neurobehavioral disorders in patients with diabetes mellitus. Studies also found an association between severity of diabetes mellitus and the progression of white matter hyperintensity on magnetic resonance imaging, which conferred...

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Main Authors: Li-Ping Wang, Jieli Geng, Chang Liu, Yuyang Wang, Zhijun Zhang, Guo-Yuan Yang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-05-01
Series:Frontiers in Aging Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnagi.2022.846739/full
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author Li-Ping Wang
Li-Ping Wang
Jieli Geng
Chang Liu
Yuyang Wang
Zhijun Zhang
Guo-Yuan Yang
author_facet Li-Ping Wang
Li-Ping Wang
Jieli Geng
Chang Liu
Yuyang Wang
Zhijun Zhang
Guo-Yuan Yang
author_sort Li-Ping Wang
collection DOAJ
description Recent clinical studies demonstrated an increase of the incidence of neurobehavioral disorders in patients with diabetes mellitus. Studies also found an association between severity of diabetes mellitus and the progression of white matter hyperintensity on magnetic resonance imaging, which conferred risk for developing cognitive impairment. Since oligodendrocyte precursor cells participated in the white matter repair and remodeling after ischemic brain injury, we explored whether hyperglycemia induced neurobehavioral deficits were associated with dysfunction of oligodendrocyte precursor cells. Adult male C57BL/6 mice (n = 40) were randomly divided into 4-week diabetes, 8-week diabetes, and control groups. Experimental diabetic mice were induced by streptozotocin injection. Learning and cognitive function, exploratory, anxiety and depression behaviors were assessed by Morris water maze, open field test, elevated plus maze, and tail suspension test, respectively. Immunofluorescence staining of neuron-glial antigen 2 and myelin basic protein were performed. Oligodendrocyte precursor cells were cultured in different glucose level to explore possible mechanism in vitro. The learning and cognitive function of 4-week and 8-week diabetic mice were attenuated compared to the control group (p < 0.05). The diabetic mice had less exploratory behavior compared to the control (p < 0.05). However, the diabetic mice were more likely to show anxiety (p < 0.05) and depression (p < 0.01) compared to the control. Further study demonstrated the number of oligodendrocyte precursor cells and the level of myelin basic protein expression were decreased in diabetic mice and the migration and survival ability were suppressed in the hyperglycemic environment in vitro (p < 0.05). Our results demonstrated that diabetes mellitus induced neurological deficits were associated with the decreased number and dysfunction of oligodendrocyte precursor cells.
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spelling doaj.art-c9a85a6128e04c3db5e48b1f023bdaae2022-12-22T00:29:32ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-05-011410.3389/fnagi.2022.846739846739Diabetes Mellitus-Related Neurobehavioral Deficits in Mice Are Associated With Oligodendrocyte Precursor Cell DysfunctionLi-Ping Wang0Li-Ping Wang1Jieli Geng2Chang Liu3Yuyang Wang4Zhijun Zhang5Guo-Yuan Yang6Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaMed-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaMed-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, ChinaMed-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaMed-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaRecent clinical studies demonstrated an increase of the incidence of neurobehavioral disorders in patients with diabetes mellitus. Studies also found an association between severity of diabetes mellitus and the progression of white matter hyperintensity on magnetic resonance imaging, which conferred risk for developing cognitive impairment. Since oligodendrocyte precursor cells participated in the white matter repair and remodeling after ischemic brain injury, we explored whether hyperglycemia induced neurobehavioral deficits were associated with dysfunction of oligodendrocyte precursor cells. Adult male C57BL/6 mice (n = 40) were randomly divided into 4-week diabetes, 8-week diabetes, and control groups. Experimental diabetic mice were induced by streptozotocin injection. Learning and cognitive function, exploratory, anxiety and depression behaviors were assessed by Morris water maze, open field test, elevated plus maze, and tail suspension test, respectively. Immunofluorescence staining of neuron-glial antigen 2 and myelin basic protein were performed. Oligodendrocyte precursor cells were cultured in different glucose level to explore possible mechanism in vitro. The learning and cognitive function of 4-week and 8-week diabetic mice were attenuated compared to the control group (p < 0.05). The diabetic mice had less exploratory behavior compared to the control (p < 0.05). However, the diabetic mice were more likely to show anxiety (p < 0.05) and depression (p < 0.01) compared to the control. Further study demonstrated the number of oligodendrocyte precursor cells and the level of myelin basic protein expression were decreased in diabetic mice and the migration and survival ability were suppressed in the hyperglycemic environment in vitro (p < 0.05). Our results demonstrated that diabetes mellitus induced neurological deficits were associated with the decreased number and dysfunction of oligodendrocyte precursor cells.https://www.frontiersin.org/articles/10.3389/fnagi.2022.846739/fullcognitionbehaviordiabetesoligodendrocyte precursor cellswhite matter
spellingShingle Li-Ping Wang
Li-Ping Wang
Jieli Geng
Chang Liu
Yuyang Wang
Zhijun Zhang
Guo-Yuan Yang
Diabetes Mellitus-Related Neurobehavioral Deficits in Mice Are Associated With Oligodendrocyte Precursor Cell Dysfunction
Frontiers in Aging Neuroscience
cognition
behavior
diabetes
oligodendrocyte precursor cells
white matter
title Diabetes Mellitus-Related Neurobehavioral Deficits in Mice Are Associated With Oligodendrocyte Precursor Cell Dysfunction
title_full Diabetes Mellitus-Related Neurobehavioral Deficits in Mice Are Associated With Oligodendrocyte Precursor Cell Dysfunction
title_fullStr Diabetes Mellitus-Related Neurobehavioral Deficits in Mice Are Associated With Oligodendrocyte Precursor Cell Dysfunction
title_full_unstemmed Diabetes Mellitus-Related Neurobehavioral Deficits in Mice Are Associated With Oligodendrocyte Precursor Cell Dysfunction
title_short Diabetes Mellitus-Related Neurobehavioral Deficits in Mice Are Associated With Oligodendrocyte Precursor Cell Dysfunction
title_sort diabetes mellitus related neurobehavioral deficits in mice are associated with oligodendrocyte precursor cell dysfunction
topic cognition
behavior
diabetes
oligodendrocyte precursor cells
white matter
url https://www.frontiersin.org/articles/10.3389/fnagi.2022.846739/full
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