女性糖尿病db/db模型中神经血管单位的超微结构重塑——第二部分:小胶质细胞和线粒体

M. Hayden, D. Grant, A. Aroor, V. DeMarco
{"title":"女性糖尿病db/db模型中神经血管单位的超微结构重塑——第二部分:小胶质细胞和线粒体","authors":"M. Hayden, D. Grant, A. Aroor, V. DeMarco","doi":"10.3390/NEUROGLIA1020021","DOIUrl":null,"url":null,"abstract":"Obesity, insulin resistance, and type 2 diabetes mellitus are associated with diabetic cognopathy. This study tested the hypothesis that neurovascular unit(s) (NVU) within cerebral cortical gray matter regions may depict abnormal cellular remodeling. The monogenic (Leprdb) female diabetic db/db [BKS.CgDock7m +/+Leprdb/J] (DBC) mouse model was utilized for this ultrastructural study. Upon sacrifice (20 weeks), left-brain hemispheres of the DBC and age-matched nondiabetic control C57BL/KsJ (CKC) mice were immediately immersion-fixed. We observed an attenuation/loss of endothelial blood–brain barrier tight/adherens junctions and pericytes, thickened basement membranes, adherent red and white blood cells, neurovascular unit microbleeds and pathologic remodeling of protoplasmic astrocytes. In this second of a three-part series, we focus on the observational ultrastructural remodeling of microglia and mitochondria in relation to the NVU in leptin receptor deficient DBC models. This study identified novel ultrastructural core signature remodeling changes, which consisted of invasive activated microglia, microglial aberrant mitochondria with nuclear chromatin condensation and adhesion of white blood cells to an activated endothelium of the NVU. In conclusion, the results implicate activated microglia in NVU uncoupling and the resulting ischemic neuronal and synaptic damage, which may be related to impaired cognition and diabetic cognopathy.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2018-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/NEUROGLIA1020021","citationCount":"21","resultStr":"{\"title\":\"Ultrastructural Remodeling of the Neurovascular Unit in the Female Diabetic db/db Model–Part II: Microglia and Mitochondria\",\"authors\":\"M. Hayden, D. Grant, A. Aroor, V. DeMarco\",\"doi\":\"10.3390/NEUROGLIA1020021\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Obesity, insulin resistance, and type 2 diabetes mellitus are associated with diabetic cognopathy. This study tested the hypothesis that neurovascular unit(s) (NVU) within cerebral cortical gray matter regions may depict abnormal cellular remodeling. The monogenic (Leprdb) female diabetic db/db [BKS.CgDock7m +/+Leprdb/J] (DBC) mouse model was utilized for this ultrastructural study. Upon sacrifice (20 weeks), left-brain hemispheres of the DBC and age-matched nondiabetic control C57BL/KsJ (CKC) mice were immediately immersion-fixed. We observed an attenuation/loss of endothelial blood–brain barrier tight/adherens junctions and pericytes, thickened basement membranes, adherent red and white blood cells, neurovascular unit microbleeds and pathologic remodeling of protoplasmic astrocytes. In this second of a three-part series, we focus on the observational ultrastructural remodeling of microglia and mitochondria in relation to the NVU in leptin receptor deficient DBC models. This study identified novel ultrastructural core signature remodeling changes, which consisted of invasive activated microglia, microglial aberrant mitochondria with nuclear chromatin condensation and adhesion of white blood cells to an activated endothelium of the NVU. In conclusion, the results implicate activated microglia in NVU uncoupling and the resulting ischemic neuronal and synaptic damage, which may be related to impaired cognition and diabetic cognopathy.\",\"PeriodicalId\":74275,\"journal\":{\"name\":\"Neuroglia (Basel, Switzerland)\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2018-10-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.3390/NEUROGLIA1020021\",\"citationCount\":\"21\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuroglia (Basel, Switzerland)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/NEUROGLIA1020021\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroglia (Basel, Switzerland)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/NEUROGLIA1020021","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 21

摘要

肥胖、胰岛素抵抗和2型糖尿病与糖尿病认知病变有关。这项研究验证了大脑皮层灰质区域内的神经血管单位(NVU)可能描述异常细胞重塑的假设。采用单基因(Leprdb)雌性糖尿病db/db[BKS.CgDock7m+/+Leprdb/J](DBC)小鼠模型进行超微结构研究。牺牲后(20周),DBC和年龄匹配的非糖尿病对照C57BL/KsJ(CKC)小鼠的左脑半球立即浸入固定。我们观察到内皮血脑屏障紧密/粘附连接和周细胞的减弱/丧失,基底膜增厚,红细胞和白细胞粘附,神经血管单位微出血和原生质星形胶质细胞的病理重塑。在这三部分系列的第二部分中,我们重点观察了瘦素受体缺陷型DBC模型中小胶质细胞和线粒体的超微结构重塑与NVU的关系。本研究确定了新的超微结构核心特征重塑变化,包括侵袭性活化的小胶质细胞、具有核染色质凝聚的小胶质异常线粒体以及白细胞与NVU活化内皮的粘附。总之,研究结果表明,活化的小胶质细胞参与NVU解偶联以及由此产生的缺血性神经元和突触损伤,这可能与认知受损和糖尿病认知病变有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Ultrastructural Remodeling of the Neurovascular Unit in the Female Diabetic db/db Model–Part II: Microglia and Mitochondria
Obesity, insulin resistance, and type 2 diabetes mellitus are associated with diabetic cognopathy. This study tested the hypothesis that neurovascular unit(s) (NVU) within cerebral cortical gray matter regions may depict abnormal cellular remodeling. The monogenic (Leprdb) female diabetic db/db [BKS.CgDock7m +/+Leprdb/J] (DBC) mouse model was utilized for this ultrastructural study. Upon sacrifice (20 weeks), left-brain hemispheres of the DBC and age-matched nondiabetic control C57BL/KsJ (CKC) mice were immediately immersion-fixed. We observed an attenuation/loss of endothelial blood–brain barrier tight/adherens junctions and pericytes, thickened basement membranes, adherent red and white blood cells, neurovascular unit microbleeds and pathologic remodeling of protoplasmic astrocytes. In this second of a three-part series, we focus on the observational ultrastructural remodeling of microglia and mitochondria in relation to the NVU in leptin receptor deficient DBC models. This study identified novel ultrastructural core signature remodeling changes, which consisted of invasive activated microglia, microglial aberrant mitochondria with nuclear chromatin condensation and adhesion of white blood cells to an activated endothelium of the NVU. In conclusion, the results implicate activated microglia in NVU uncoupling and the resulting ischemic neuronal and synaptic damage, which may be related to impaired cognition and diabetic cognopathy.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Comparison of the Transduction Capacity of AAV5 and AAV PHP.eB Serotypes in Hippocampus Astroglia The Signaling of Neuregulin-Epidermal Growth Factor Receptors and Its Impact on the Nervous System GABAA-ρ Receptors in the CNS: Their Functional, Pharmacological, and Structural Properties in Neurons and Astroglia Combination of Engineered Expression of Polysialic Acid on Transplanted Schwann Cells and in Injured Rat Spinal Cord Promotes Significant Axonal Growth and Functional Recovery Glucose Transporter-2 Regulation of Male versus Female Hypothalamic Astrocyte MAPK Expression and Activation: Impact of Glucose.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1