Severe Hypoglycemia Contributing to Cognitive Dysfunction in Diabetic Mice Is Associated With Pericyte and Blood–Brain Barrier Dysfunction

Background: Severe hypoglycemia can cause cognitive impairment in diabetic patients, but the underlying molecular mechanism remains unclear.Objective: To assess the effect of severe hypoglycemia on cognitive function in diabetic mice to clarify the relationship between the mechanism and dysfunction...

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Autores principales:	Lu Lin, Yubin Wu, Zhou Chen, Lishan Huang, Lijing Wang, Libin Liu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	severe hypoglycemia diabetes mellitus cognitive dysfunction pericyte blood–brain barrier Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/1d6f1d17f96e4cbda785497a3477fc04
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spelling	oai:doaj.org-article:1d6f1d17f96e4cbda785497a3477fc042021-12-01T08:20:59ZSevere Hypoglycemia Contributing to Cognitive Dysfunction in Diabetic Mice Is Associated With Pericyte and Blood–Brain Barrier Dysfunction1663-436510.3389/fnagi.2021.775244https://doaj.org/article/1d6f1d17f96e4cbda785497a3477fc042021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.775244/fullhttps://doaj.org/toc/1663-4365Background: Severe hypoglycemia can cause cognitive impairment in diabetic patients, but the underlying molecular mechanism remains unclear.Objective: To assess the effect of severe hypoglycemia on cognitive function in diabetic mice to clarify the relationship between the mechanism and dysfunction of pericytes and the blood–brain barrier (BBB).Method: We established type 1 diabetes mellitus in 80 male C57BL/6J mice by intraperitoneal injection of streptozotocin (150 mg/kg). Further intraperitoneal injection of short-acting insulin induced severe hypoglycemia. The mice were divided into normal, diabetes, and diabetic + severe hypoglycemia groups, and their blood glucose and general weight index were examined. Pericyte and BBB morphology and function were detected by histological and western blot analyses, BBB permeability was detected by Evans blue staining, and cognitive function was detected with the Morris water maze.Results: Severe hypoglycemia aggravated the histological damage, BBB damage, brain edema, and pericyte loss in the diabetic mice. It also reduced the expression of the BBB tight junction proteins occludin and claudin-5, the expression of the pericyte-specific markers PDGFR-β (platelet-derived growth factor receptor-β) and α-SMA, and increased the expression of the inflammatory factor MMP9. At the same time, diabetic mice with severe hypoglycemia had significantly reduced cognitive function.Conclusion: Severe hypoglycemia leads to cognitive dysfunction in diabetic mice, and its possible mechanism is related to pericyte dysfunction and BBB destruction.Lu LinYubin WuZhou ChenLishan HuangLijing WangLibin LiuFrontiers Media S.A.articlesevere hypoglycemiadiabetes mellituscognitive dysfunctionpericyteblood–brain barrierNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	severe hypoglycemia diabetes mellitus cognitive dysfunction pericyte blood–brain barrier Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	severe hypoglycemia diabetes mellitus cognitive dysfunction pericyte blood–brain barrier Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Lu Lin Yubin Wu Zhou Chen Lishan Huang Lijing Wang Libin Liu Severe Hypoglycemia Contributing to Cognitive Dysfunction in Diabetic Mice Is Associated With Pericyte and Blood–Brain Barrier Dysfunction
description	Background: Severe hypoglycemia can cause cognitive impairment in diabetic patients, but the underlying molecular mechanism remains unclear.Objective: To assess the effect of severe hypoglycemia on cognitive function in diabetic mice to clarify the relationship between the mechanism and dysfunction of pericytes and the blood–brain barrier (BBB).Method: We established type 1 diabetes mellitus in 80 male C57BL/6J mice by intraperitoneal injection of streptozotocin (150 mg/kg). Further intraperitoneal injection of short-acting insulin induced severe hypoglycemia. The mice were divided into normal, diabetes, and diabetic + severe hypoglycemia groups, and their blood glucose and general weight index were examined. Pericyte and BBB morphology and function were detected by histological and western blot analyses, BBB permeability was detected by Evans blue staining, and cognitive function was detected with the Morris water maze.Results: Severe hypoglycemia aggravated the histological damage, BBB damage, brain edema, and pericyte loss in the diabetic mice. It also reduced the expression of the BBB tight junction proteins occludin and claudin-5, the expression of the pericyte-specific markers PDGFR-β (platelet-derived growth factor receptor-β) and α-SMA, and increased the expression of the inflammatory factor MMP9. At the same time, diabetic mice with severe hypoglycemia had significantly reduced cognitive function.Conclusion: Severe hypoglycemia leads to cognitive dysfunction in diabetic mice, and its possible mechanism is related to pericyte dysfunction and BBB destruction.
format	article
author	Lu Lin Yubin Wu Zhou Chen Lishan Huang Lijing Wang Libin Liu
author_facet	Lu Lin Yubin Wu Zhou Chen Lishan Huang Lijing Wang Libin Liu
author_sort	Lu Lin
title	Severe Hypoglycemia Contributing to Cognitive Dysfunction in Diabetic Mice Is Associated With Pericyte and Blood–Brain Barrier Dysfunction
title_short	Severe Hypoglycemia Contributing to Cognitive Dysfunction in Diabetic Mice Is Associated With Pericyte and Blood–Brain Barrier Dysfunction
title_full	Severe Hypoglycemia Contributing to Cognitive Dysfunction in Diabetic Mice Is Associated With Pericyte and Blood–Brain Barrier Dysfunction
title_fullStr	Severe Hypoglycemia Contributing to Cognitive Dysfunction in Diabetic Mice Is Associated With Pericyte and Blood–Brain Barrier Dysfunction
title_full_unstemmed	Severe Hypoglycemia Contributing to Cognitive Dysfunction in Diabetic Mice Is Associated With Pericyte and Blood–Brain Barrier Dysfunction
title_sort	severe hypoglycemia contributing to cognitive dysfunction in diabetic mice is associated with pericyte and blood–brain barrier dysfunction
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/1d6f1d17f96e4cbda785497a3477fc04
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Severe Hypoglycemia Contributing to Cognitive Dysfunction in Diabetic Mice Is Associated With Pericyte and Blood–Brain Barrier Dysfunction

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