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
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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。
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.
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